| 1. |
- Abdalla-Elsayed, Maram E.A., et al.
(author)
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Heterozygous mutation in OTX2 associated with early-onset retinal dystrophy with atypical maculopathy
- 2017
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In: Molecular Vision. - 1090-0535. ; 23, s. 778-784
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Journal article (peer-reviewed)abstract
- Purpose: Heterozygous mutations in OTX2 have been associated with a range of ocular and pituitary abnormalities. We report a novel heterozygous deletion in OTX2 underlying early-onset retinal dystrophy with atypical maculopathy. Methods: Clinical examination included electroretinography and multimodal retinal imaging. Molecular genetic testing was composed of next-generation sequencing of a panel of retinal dystrophy genes. Results: A now 17-year-old boy presented 12 years earlier with a history of progressively poor vision since birth, nyctalopia, and early-onset retinal dystrophy with atypical maculopathy. He also had bilateral microphthalmos and a slim prepubertal appearance; growth hormone levels were within normal ranges. Next-generation sequencing of a retinal dystrophy gene panel revealed a heterozygous deletion c.485delC (p.Pro162G.Infs*24) in exon 5 of OTX2. Conclusions: This second report of maculopathy associated with a heterozygous mutation in OTX2 confirms that mutations in OTX2 should be considered in the differential diagnosis of atypical hereditary maculopathy, with or without rod-cone dystrophy.
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| 2. |
- Abdalla Elsayed, Maram E.A., et al.
(author)
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Incidence of Intraocular Lens Exchange after Cataract Surgery
- 2019
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1
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Journal article (peer-reviewed)abstract
- Intraocular lens (IOL) exchange after cataract surgery is unusual but may be associated with suboptimal visual outcome. The incidence of IOL exchange has not been consistently estimated. Such information is invaluable when counseling patients prior to cataract surgery. We examined the incidence of, and indications and risk factors for, IOL exchange after cataract surgery. We also assessed visual outcome of eyes that had an IOL exchange. A cohort design was used to estimate the incidence of IOL exchange and a case-control design to identify factors associated with it. All phacoemulsification surgeries with IOL (n = 17415 eyes) during 2010-2017 and those that had a subsequent IOL removal or replacement during the same time period were identified (n = 34 eyes). The incidence of IOL exchange was 2 per 1000 surgeries (95% confidence interval [CI] 1 to 3) over 8 years. Eyes that underwent subsequent IOL removal or replacement were compared with eyes that had cataract surgery only (n = 47) across demographic and clinical characteristics. In a binary logistic regression analysis, two factors were significantly associated with IOL exchange/removal: an adverse event during cataract surgery (adjusted odds ratio [aOR] 19.45; 95% CI 4.89-77.30, P < 0.001) and a pre-existing ocular comorbidity (aOR 10.70; 95% CI 1.69-67.63, P = 0.021). The effect of gender was marginally significant (P = 0.077). Eyes that underwent IOL exchange or explantation were nearly two and a half times more likely to have a final best-corrected visual acuity of <20/60 compared to those that had cataract surgery alone (adjusted RR 2.60 95% CI, 1.13-6.02; P = 0.025).
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| 3. |
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| 4. |
- Abdalla Elsayed, Maram E.A., et al.
(author)
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Sickle cell retinopathy. A focused review
- 2019
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In: Graefe's Archive for Clinical and Experimental Ophthalmology. - : Springer Science and Business Media LLC. - 0721-832X .- 1435-702X. ; 257:7, s. 1353-1364
-
Research review (peer-reviewed)abstract
- Purpose: To provide a focused review of sickle cell retinopathy in the light of recent advances in the pathogenesis, multimodal retinal imaging, management of the condition, and migration trends, which may lead to increased prevalence of the condition in the Western world. Methods: Non-systematic focused literature review. Results: Sickle retinopathy results from aggregation of abnormal hemoglobin in the red blood cells in the retinal microcirculation, leading to reduced deformability of the red blood cells, stagnant blood flow in the retinal precapillary arterioles, thrombosis, and ischemia. This may be precipitated by hypoxia, acidosis, and hyperosmolarity. Sickle retinopathy may result in sight threatening complications, such as paracentral middle maculopathy or sequelae of proliferative retinopathy, such as vitreous hemorrhage and retinal detachment. New imaging modalities, such as wide-field imaging and optical coherence tomography angiography, have revealed the microstructural features of sickle retinopathy, enabling earlier diagnosis. The vascular growth factor ANGPTL-4 has recently been identified as a potential mediator of progression to proliferative retinopathy and may represent a possible therapeutic target. Laser therapy should be considered for proliferative retinopathy in order to prevent visual loss; however, the evidence is not very strong. With recent development of wide-field imaging, targeted laser to ischemic retina may prove to be beneficial. Exact control of intraoperative intraocular pressure, including valved trocar vitrectomy systems, may improve the outcomes of vitreoretinal surgery for complications, such as vitreous hemorrhage and retinal detachment. Stem cell transplantation and gene therapy are potentially curative treatments, which may prevent retinopathy. Conclusions: There is lack of evidence regarding the optimal management of sickle retinopathy. Further study is needed to determine if recent progress in the understanding of the pathophysiology and diagnosis of sickle retinopathy may translate into improved management and outcome.
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| 5. |
- Abdelkader, Ehab, et al.
(author)
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Analysis of retinal structure and function in cone dystrophy with supernormal rod response
- 2020
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In: Documenta Ophthalmologica. - : Springer Science and Business Media LLC. - 0012-4486 .- 1573-2622.
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Journal article (peer-reviewed)abstract
- Purpose: To report the clinical and electrophysiological features of cone dystrophy with supernormal rod response (CDSRR). Methods: Retrospective cohort study of 15 unrelated patients (nine males and six females, median age 16, range 5–47 years) diagnosed with CDSRR by clinical examination, full-field electroretinography (ERG) and genetic testing. Observations: History, ophthalmic examination including near vision, color vision and contrast sensitivity assessment, multimodal retinal imaging and ERG. Genetic testing was done for all patients using next-generation sequencing. Results: The rate of consanguinity was 86.7%. Color vision was defective in 56.3%. Near vision was defective in all patients (mean 20/160). Contrast sensitivity was affected in all patients at low contrast of 2.5%. A parafoveal ring of increased autofluorescence imaging was seen in most patients (75%). Supernormal mixed maximal response b-wave was seen bilaterally in 63% of patients (and high normal in 37%). Rod dysfunction with prolonged rod b-wave latency was detected in all. The 30-Hz flicker response was more reduced and delayed compared to the single-flash cone response. A novel homozygous missense variant c.530G>C (p.Cys177Ser) in KCNV2 was detected in one patient, the nonsense homozygous mutation c.427G>T (p.Glu143*) was found in 13 patients, and the nonsense c.159C>G (p.Tyr53*) was found in one patient. Conclusion: This is the largest cohort of CDSRR from a single ethnic background. Rod dysfunction and reduced 30-Hz flicker response were demonstrated in all patients. In contrast to previous descriptions in the literature, a supernormal combined dark-adapted rod-cone ERG was present in the majority of the patients at standard stimulus intensity. Considering the consistent genotype and the demonstration of likely pathogenic genetic variants in all the patients, we argue that the combination of delayed rod b-wave and subnormal flicker response strongly suggests the diagnosis of CDSRR.
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| 6. |
- Abdelkader, Ehab, et al.
(author)
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Novel causative variants in patients with achromatopsia
- 2018
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In: Ophthalmic Genetics. - : Informa UK Limited. - 1381-6810 .- 1744-5094. ; 39:6, s. 678-683
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Journal article (peer-reviewed)abstract
- Purpose: To report five novel genetic variants in seven unrelated consanguineous families with achromatopsia (ACHM). Methods: Patients were examined with multimodal retinal imaging and full-field electroretinography (ffERG). Genetic testing was conducted using next-generation sequencing (NGS). Results: Three novel homozygous variants were detected in CNGA3: a missense c.967G > C (p.Ala323Pro) variant was detected in exon 8 (one patient), a splice site variant c.101 + 1G > A in intron 2 (three patients), and a splice site variant c.395 + 1G > T in intron 4(one patient). Another two novel variants were found in PDE6C: a homozygous missense variant c.1899C > A (p.His633Gln) in exon 15 (one patient) and a homozygous splice site variant c.1072-1G > C in intron 7 (one patient). Mutation segregation assessment was possible in 3 of the 7 families. All patients had nonrecordable ffERG 30-Hz flicker responses, reduced single-flash cone responses but preserved rod responses. Patients presented with variable degrees of foveal outer retinal layer loss and variable patterns of foveal hyperautofluorescence. Conclusions: These novel variants expand the genotypes associated with ACHM and may help in future therapy development for ACHM.
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| 7. |
- Abdelkader, Ehab, et al.
(author)
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Severe retinal degeneration at an early age in Usher syndrome type 1B associated with homozygous splice site mutations in MYO7A gene
- 2018
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In: Saudi Journal of Ophthalmology. - : Medknow. - 1319-4534. ; 32:2, s. 119-125
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Journal article (peer-reviewed)abstract
- Purpose: Usher syndrome is the most common cause of deafness associated with visual loss of a genetic origin. The purpose of this paper is to report very severe phenotypic features of type 1B Usher syndrome in a Saudi family affected by positive homozygous splice site mutation in MYO7A gene. Methods: Affected siblings went through detailed history. Complete ophthalmic examination was done. Imaging with colour fundus photography, fundus autofluorescence (AF), and optical coherence tomography (OCT) scans was performed. Full field electroretinogram (ffERG) was recorded. Molecular genetic testing was done using next-generation sequencing. Results: Visual acuity was more reduced (range 20/300–20/40) in older siblings (age>30 years), than in younger (age <30 years) siblings (range 20/70–20/25). OCT scans showed macular atrophy in all but one case that has cystoid macular edema (CME). AF demonstrated atrophy outside a small foveal area showing high signal. FfERG was flat in all cases. The homozygous splice site mutation c.470+1G>A in intron 5 of the MYO7A gene was detected in all affected siblings. Conclusions: This mutation manifested with advanced retinal degeneration at a young age. This may have implications regarding future gene therapy in Usher syndrome cases with this genotype.
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| 8. |
- Al Akeely, Adel, et al.
(author)
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Electrophysiological evaluation of fleck retina and temporal macular thinning in X-Linked alport's syndrome
- 2021
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In: Middle East African Journal of Ophthalmology. - : Medknow. - 0974-9233. ; 28:4, s. 257-259
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Journal article (peer-reviewed)abstract
- We report a 39-year-old with Alport's syndrome. The patient presented with anterior lenticonus, cataract, and a corrected distance visual acuity of 20/25 and 20/60 in the right and left eyes, respectively. Fundus examination revealed generalized retinal flecks sparing the fovea in both eyes. Optical coherence topography showed temporal macular thinning. Normal fundus autofluorescence was observed in both eyes. Full-field electroretinography (ERG) demonstrated normal photopic and scotopic responses, while multifocal ERG showed no reduction of amplitudes generated from the temporal thinned macula, compared to the nasal macula, indicating preserved functional integrity of the retina.
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| 9. |
- Al-Barki, Abdulrahman, et al.
(author)
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Comparison of short-pulse subthreshold (532 nm) and infrared micropulse (810 nm) macular laser for diabetic macular edema
- 2021
-
In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1
-
Journal article (peer-reviewed)abstract
- The purpose of the study was to assess both anatomic and functional outcomes between short-pulse continuous wavelength and infrared micropulse lasers in the treatment of DME. This was a prospective interventional study from tertiary care eye hospital—King Khaled Eye Specialist Hospital (Riyadh, Saudi Arabia). Patients with center-involving diabetic macular edema were treated with subthreshold laser therapy. Patients in the micropulse group were treated with the 810-nm diode micropulse scanning laser TxCell (IRIDEX Corporation, Mountain View, CA, USA) (subthreshold micropulse—STMP group). Laser was applied according to recommendations for MicroPulse (125 microns spot size, 300 ms pulse duration and power adjustment following barely visible testing burn) in a confluent mode (low intensity/high density) to the entire area of the macular edema. Patients in the short-pulse group were treated with grid pattern laser with 20 ms pulse PASCAL laser 532 nm (TopCon Medical Laser Systems, Tokyo, Japan) with EndPoint algorithm, which was either 30% or 50% of testing burn (EndPoint 30% and EndPoint 50% groups, respectively). Main outcome measures included best-corrected visual acuity (BCVA in logMAR) and foveal thickness at baseline and the last follow-up visit at 6 months. There were 44 eyes in the micropulse group, 54 eyes in the EndPoint 50% group and 18 eyes in the EndPoint 30% group. BCVA for the whole cohort (logMAR) was 0.451 (Snellen equivalent 20/56) at baseline, 0.495 (Snellen equivalent 20/62) (p = 0.053) at 3 months, and 0.494 (Snellen equivalent 20/62) at the last follow-up (p = 0.052). Foveal thickness for the whole cohort was 378.2 ± 51.7 microns at baseline, 347.2 ± 61.3 microns (p = 0.002) at 3 months, and 346.0 ± 24.6 microns at the final follow-up (p = 0.027). As such the short-pulse system yields more temporary reduction in edema. Comparison of BCVA between baseline and 6 months for EndPoint 30%, EndPoint 50% and STMP groups was p = 0.88, p = 0.76 and p = 0.003, respectively. Comparison of foveal thickness between baseline and 6 months for EndPoint 30%, EndPoint 50% and STMP groups was p = 0.38, p = 0.22 and p = 0.14, respectively. We conclude that the infrared micropulse system seems to improve functional outcomes. When applied according to previously published reports, short-pulse system may yield more temporary reduction in edema while infrared micropulse system may yield slightly better functional outcomes.
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| 10. |
- Al-Hujaili, Haneen, et al.
(author)
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Long-term follow-up of retinal function and structure in trpm1-associated complete congenital stationary night blindness
- 2019
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In: Molecular Vision. - 1090-0535. ; 25, s. 851-858
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Journal article (peer-reviewed)abstract
- Purpose: TRPM1-associated congenital stationary night blindness (CSNB) is characterized by nystagmus and high myopia. We assessed retinal function and structure over long-term follow-up up to 10 years in two siblings from a family with the homozygous deletion c.2394delC in exon 18 that we previously identified. In addition, we describe retinal function and structure in two other siblings with the novel homozygous c.1394T>A (p.Met465Lys) missense mutation. Methods: Clinical examination included full-field electroretinography, axial length measurements, and multimodal retinal imaging. Molecular genetic tests included next-generation sequencing and Sanger sequencing. Results: All patients had non-recordable rod responses and electronegative configuration of the rod-cone responses at presentation. There was a median of 26% reduction in the dark-and light-adapted electroretinographic (ERG) amplitudes over 4 years. Myopia progressed rapidly in childhood but showed only a mild progression after the teenage years. Visual acuities were stable over time, and there was no sign of progressive retinal thinning. All patients had axial myopia. A novel homozygous c.1394T>A (p.Met465Lys) missense mutation in TRPM1 was identified in two siblings. Conclusions: Further prospective study in larger samples is needed to establish whether there is progressive retinal degeneration in TRPM1-associated CSNB. The associated myopia was found to be mainly axial, which has not been described previously. The mechanism of myopia development in this condition remains incompletely understood; however, it may be related to altered retinal dopamine signaling and amacrine cell dysfunction.
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| 11. |
- Al Oreany, Abdulaziz Abdulrahman, et al.
(author)
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Congenital stationary night blindness with hypoplastic discs, negative electroretinogram and thinning of the inner nuclear layer
- 2016
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In: Graefe's Archive for Clinical and Experimental Ophthalmology. - : Springer Science and Business Media LLC. - 0721-832X .- 1435-702X. ; 254:10, s. 1951-1956
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Journal article (peer-reviewed)abstract
- Purpose: To describe congenital stationary night blindness (CSNB) with negative electroretinogram, hypoplastic discs, nystagmus and thinning of the inner nuclear layer (INL). Methods: Retinal structure was analyzed qualitatively with spectral domain optical coherence tomography and wide field imaging. Retinal function was evaluated with full-field electroretinography (ffERG). Molecular genetic testing included next-generation sequencing (NGS) of the known genes involved in CSNB. Results: Patients presented with CSNB presented with nystagmus, high myopia, hypoplastic discs and negative ffERG with no measurable rod response. The retinas appeared normal and automated segmentation of retinal layers demonstrated a relative reduction of thickness of the INL. There was no significant change in the ffERG after prolonged 2 hour dark adaptation compared to standard 30 minute dark adaptation. Affected family members harboured the homozygous 1-bp deletion c.2394delC in exon 18 of the TRPM1 gene, whereas their unaffected parents were heterozygous carriers. Conclusions: This data expands the genotype and phenotype spectrum of CSNB. The lack of improvement of rod responses after prolonged dark adaptation, together with thinning of the INL, is compatible with postreceptoral transmission dysfunction in the bipolar cells. Such knowledge may prove useful in future development of treatment for outer retinal dystrophies, using opsin genes to restore light responses in survivor neurons in the inner retina.
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| 12. |
- Al-Shehri, Abdulaziz Mohammed, et al.
(author)
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Effect of silicone oil versus gas tamponade on macular layer microstructure after pars plana vitrectomy for macula on rhegmatogenous retinal detachment
- 2024
-
In: BMC Ophthalmology. - 1471-2415. ; 24:1
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Journal article (peer-reviewed)abstract
- Purpose: To analyze structural changes in the macular retinal layers and sub-foveal choroidal thickness (SFCT) in eyes after macula-on rhegmatogenous retinal detachment (RRD) repair by pars plana vitrectomy with either silicone oil (SO) or gas tamponade, and the effect of these changes on visual acuity. Patients and methods: Retrospective study which included 26 eyes in the SO Group and 32 in the Gas Group. Optical coherence tomography (OCT) scans of the affected eyes were obtained before surgery, and 3 months after PPV in the Gas Group, and during silicone oil in situ and 3 months after SO removal, in the SO Group. Qualitative assessment of photoreceptor layer and foveal contour, along with quantitative assessment of macular retinal thickness and SFCT was performed. Postoperative OCT macular microstructural changes were recorded and correlated to corrected distance visual acuity (CDVA). Intraocular pressure (IOP) was measured preoperative and at 3 months post operative. Results: There was a 2-line loss (from 20/28 preoperatively to 20/40 at final follow-up) of CDVA in the SO Group (p=0.051), while there was no statistically significant change in CDVA in the Gas Group (p=0.786). There was no significant correlation between CDVA loss and duration of silicon tamponade (r=-0.031, p=0.893). There was a statistically significant increase in IOP from its baseline to final follow-up of 0.7 mmHg in the SO Group (p=0.023) while there was no statistically significant change in IOP in the Gas Group. During silicone oil tamponade, there was approximately 11% and 5% of retinal and sub-foveal choroidal thinning respectively, which was moderately resolved following silicone oil removal. 20% (5/24) of eyes in the SO Group had qualitative flattening of foveal contour during SO tamponade that resolved after SO removal. Conclusion: Thinning of the macula was noticed after macula-on RRD repair with SO tamponade. Such thinning was only partially reversible after the removal of SO.
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| 13. |
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| 14. |
- Albabtain, Budoor, et al.
(author)
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Comparison of posterior hyaloid assessment using preoperative optical coherence tomography and intraoperative triamcinolone acetonide staining during vitrectomy
- 2021
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In: Clinical Ophthalmology. - 1177-5467. ; 15, s. 3939-3945
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Journal article (peer-reviewed)abstract
- Purpose: To compare the specificity of diagnosing posterior vitreous detachment (PVD) using preoperative optical coherence tomography (OCT) versus intraoperative triamcinolone acetonide (TA) staining in patients undergoing vitrectomy. Patients and Methods: This retrospective cohort study included patients undergoing pars plana vitrectomy for diverse retinal pathologies. Intraoperatively, surgeons evaluated the posterior hyaloid status with TA staining and compared it with preoperative OCT findings. Results: One hundred six patients underwent intraoperative assessments of posterior hyaloid status, with 72% (76/106) of the eyes showing positive staining. Sixty-two patients had also undergone preoperative OCT. Of the patients diagnosed with PVD on preoperative OCT, 50% (15/30) showed positive TA staining intraoperatively. The sensitivity of preoperative OCT assessment was 83.3%, and its specificity was 65.9%. Conclusion: Preoperative OCT imaging is associated with lower sensitivity and specificity for diagnosing PVD when compared to intraoperative TA staining.
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| 15. |
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| 16. |
- Alduaij, Atheer Ali, et al.
(author)
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Unilateral central retinal vein occlusion as a first manifestation of diabetes mellitus in a ten-year-old girl
- 2018
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In: Saudi Journal of Ophthalmology. - : Medknow. - 1319-4534. ; 32:4, s. 346-348
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Journal article (peer-reviewed)abstract
- Central retinal vein occlusion (CRVO) is relatively rare in the pediatric age group. We present a case of CRVO as the first manifestation of diabetes mellitus in a ten-year-old girl. The associated macular edema was managed successfully with a single injection of Ranibizumab. Ophthalmologists should consider the possibility of diabetes mellitus in pediatric cases of CRVO.
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| 17. |
- Almutairi, Faris, et al.
(author)
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Congenital stationary night blindness : an update and review of the disease spectrum in Saudi Arabia
- 2021
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In: Acta Ophthalmologica. - : Wiley. - 1755-375X .- 1755-3768. ; 99:6, s. 581-591
-
Research review (peer-reviewed)abstract
- Congenital stationary night blindness (CSNB) is a group of rare, mainly stationary disorders of the retina, resulting from dysfunction of several specific and essential visual processing mechanisms. The inheritance is often recessive and as such, CSNB may be more common among populations with a high degree of consanguinity. Here, we present a topic update and a review of the clinical and molecular genetic spectrum of CSNB in Saudi Arabia. Since a major review article on CSNB in 2015, which described 17 genes underlying CSNB, an additional four genes have been incriminated in autosomal recessive CSNB: RIMS2, GNB3, GUCY2D and ABCA4. These have been associated with syndromic cone–rod synaptic disease, ON bipolar cell dysfunction with reduced cone sensitivity, CSNB with dysfunction of the phototransduction (Riggs type) and CSNB with cone–rod dystrophy, respectively. In Saudi Arabia, a total of 24 patients with CSNB were identified, using a combination of literature search and retrospective study of previously unpublished cases. Recessive mutations in TRPM1 and CABP4 accounted for the majority of cases (5 and 13 for each gene, respectively). These genes were associated with complete (cCSNB) and incomplete (icCSNB), respectively, and were associated with high myopia in the former and hyperopia in the latter. Four novel mutations were identified. For the first time, we describe the fundus albipunctatus in two patients from Saudi Arabia, caused by recessive mutation in RDH5 and RPE65, where the former in addition featured findings compatible with cone dystrophy. No cases were identified with any dominantly inherited CSNB.
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| 18. |
- Alsalamah, Abrar K., et al.
(author)
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Recognizable Patterns of Submacular Fibrosis in Enhanced S-Cone Syndrome
- 2021
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In: Ophthalmology Retina. - : Elsevier BV. - 2468-6530. ; 5:9, s. 918-927
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Journal article (peer-reviewed)abstract
- Purpose: To highlight recognizable patterns of subretinal fibrosis in enhanced S-cone syndrome (ESCS). Design: Retrospective case series. Participants: Forty-seven patients with subretinal fibrosis identified from 101 patients with clinically diagnosed ESCS, confirmed by full-field electroretinography (35/47), genetic testing (34/47), or both. Methods: Multimodal retinal imaging, electroretinography, and genetic analysis. Main Outcome Measures: Patterns of subretinal fibrosis with angiographic, OCT, and genetic correlations. Results: Eighty-five eyes of 47 patients (24 male patients; 36 unrelated consanguineous families) had subretinal fibrosis. Mean age at presentation was 14 years. Best-corrected visual acuity ranged from 20/20 to hand movements. All 34 genetically tested patients were homozygous for pathogenic NR2E3 variants. Subretinal fibrosis was always in the macular area, although it extended beyond in some patients. Six recurrent patterns of submacular fibrosis were noted: central unifocal nodular, circumferential unifocal nodular, multifocal nodular, arcuate, helicoid, and thick geographic. Some patients showed a combination of patterns. Previous misdiagnosis as inflammatory disease was common. Fibrosis was fairly symmetrical in a given patient but not always present or identical in other affected individuals with a given homozygous mutation from the same or other families. Conclusions: These recognizable patterns of submacular fibrosis are part of the ESCS phenotypic spectrum and strongly suggest the disease. In addition to facilitating diagnosis, recognition of these patterns can spare patients unnecessary workup for an inflammatory cause.
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| 19. |
- Alsulaiman, Hamad M., et al.
(author)
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DIFFUSE RETINAL VASCULAR LEAKAGE AND CONE-ROD DYSTROPHY IN A FAMILY WITH THE HOMOZYGOUS MISSENSE C.1429G>A (P.GLY477ARG) MUTATION IN CRB1
- 2020
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In: Retinal Cases & Brief Reports. - 1935-1089. ; 14:2, s. 203-210
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Journal article (peer-reviewed)abstract
- PURPOSE: To describe a specific cone-rod dystrophy phenotype in a family with the homozygous c.1429G>A; p.Gly477Arg mutation in CRB1. The detailed phenotype of subjects with this specific mutation has not been described previously. METHODS: Clinical examination included full-field electroretinography and high-resolution and widefield retinal imaging and uveitis workup. Molecular genetic analysis included next-generation sequencing of known retinal dystrophy genes and Sanger sequencing for segregation analysis. RESULTS: Three affected male siblings (26, 16, and 8 years old) were diagnosed with cone-rod dystrophy, featuring bilateral macular hypoautofluorescent lesions. In addition, the eldest brother was found to have retinal vascular leakage throughout the retina without telangiectasia. Uveitis laboratory workup was unremarkable. The homozygous c.1429G>A; p.Gly477Arg mutation in CRB1 was found to segregate with disease in this family. CONCLUSION: To the best of our knowledge, diffuse vascular leakage without telangiectasia or exudation, with bull's eye maculopathy, has not been reported previously in CRB1-cone rod dystrophy. This expands the phenotype complexity associated with CRB1 mutations and confirms that dystrophies associated with mutations in this gene may appear with features of uveitis.
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| 20. |
- AlZaid, Abdulrahman, et al.
(author)
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Long-term resolution of chronic macular edema after a single dose of intravitreal dexamethasone in familial retinal arterial macroaneurysm
- 2020
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In: Ophthalmic Genetics. - : Informa UK Limited. - 1381-6810 .- 1744-5094. ; 41:4, s. 394-396
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Journal article (peer-reviewed)abstract
- Purpose: To report a favorable effect of intravitreal dexamethasone implantation in Familial Retinal Arterial Macroaneurysms (FRAM). Methods: Retrospective Case Report. Results: A 32-year-old male who presented with bilateral retinal macroaneurysms. Whole Exome Sequencing (WES) revealed a homozygous c.830–1 G > A mutation in Insulin Growth Factor Binding Protein 7 (IGFBP7) gene, confirming the diagnosis FRAM. The left eye was lost in the course of the disease, whereas the right eye developed a persistent macular edema due to multiple leaking retinal arterial macroaneurysms and responded poorly to intravitreal ranibizumab and only partially to intravitreal aflibercept. Intravitreal dexamethasone implantation in the right eye, on the other hand, resulted in marked visual and structural improvement. Conclusion: Intravitreal dexamethasone injections have beneficial anatomical and visual outcomes in FRAM patients with persistent macular edema poorly responsive to intravitreal injections.
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| 21. |
- Badawi, Abdulrahman, et al.
(author)
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Cone dystrophy associated with autoimmune polyglandular syndrome type 1
- 2023
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In: Scientific Reports. - 2045-2322. ; 13:1
-
Journal article (peer-reviewed)abstract
- To report the association of autoimmune polyglandular syndrome type 1 (APS1) with cone dystrophy in a large Saudi family. This is a Retrospective chart review and prospective genetic testing and ophthalmic examination of a large multiplex consanguineous family. Genetic testing was performed on 14 family members, seven of whom had detailed ophthalmic examinations. Medical history, ocular history and evaluation, visual field testing, full-field electroretinogram (ERG), and Whole Exome Sequencing (WES) results were analyzed. Three family members were homozygous for c.205_208dupCAGG;p.(Asp70Alafs*148) in AIRE and homozygous for c.481-1G>A in PDE6C. One additional family member was homozygous for only the AIRE variant and another additional family member was homozygous for only the PDE6C variant. All patients with homozygosity for the PDE6C variant had cone dystrophy, and all patients with homozygosity for the AIRE variant had APS1. In addition, two of the family members who were homozygous for the PDE6C and AIRE variants had reduced rod function on ERG. We report the co-inheritance for APS1 and PDE6C-related cone dystrophy, an unusual example of two seemingly independent recessive conditions coinciding within a family. Dual molecular diagnosis must be taken into account by ophthalmologists facing unusual constellations of findings, especially in consanguineous families.
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| 22. |
- Bitner, Hanna, et al.
(author)
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Frequency, Genotype, and Clinical Spectrum of Best Vitelliform Macular Dystrophy: Data From a National Center in Denmark
- 2012
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In: American Journal of Ophthalmology. - : Elsevier BV. - 1879-1891 .- 0002-9394. ; 154:2, s. 403-412
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Journal article (peer-reviewed)abstract
- PURPOSE: To estimate the prevalence, genotype, and clinical spectrum of Best vitelliform macular dystrophy (Best disease). DESIGN: Retrospective epidemiologic and clinical and molecular genetic observational study. METHODS: SETTING: National referral center. PARTICIPANTS: Forty-five individuals diagnosed with Best disease. OBSERVATION PROCEDURES: Retrospective review of patients diagnosed according to clinical findings and sequencing of BEST1. Patients with recently established molecular genetic diagnosis were followed up including multifocal electroretinography (mfERG), spectral-domain optical coherence tomography (SD-OCT), and fundus autofluorescence (FAF) imaging. MAIN OUTCOME MEASURES: BEST1 mutations, SD-OCT and FAF findings, mfERG amplitudes, prevalence estimate of Best disease. RESULTS: BEST1 mutations described previously in Danish patients with Best disease are reviewed. In addition, we identified a further 8 families and 1 sporadic case, in whom 6 BEST1 missense mutations were found, 4 of which are novel. The mutation c.904G>T (p.Asp302Asn) was identified in members of 4 unrelated families. Structural alterations ranged from precipitate-like alterations at the level of the photoreceptor outer segments (OS) to choroidal neovascularization. The extent of the former correlated with the reduction of retinal function. A prevalence estimate of Best disease in Denmark based on the number of diagnosed cases was 1.5 per 100 000 individuals. CONCLUSIONS: Our data expand the mutation spectrum of BEST1 in patients with Best disease. Alterations of the OS overlying lesions with subretinal fluid are similar to those seen in central serous retinopathy and may indicate impaired turnover of OS. Our frequency estimate confirms that Best disease is one of the most common causes of early macular degeneration. (Am J Ophthalmol 2012;154:403-412. (c) 2012 by Elsevier Inc. All rights reserved.)
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| 23. |
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| 24. |
- Galvez-Ruiz, Alberto, et al.
(author)
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Genetic Testing for Wolfram Syndrome Mutations in a Sample of 71 Patients with Hereditary Optic Neuropathy and Negative Genetic Test Results for OPA1/OPA3/LHON
- 2018
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In: Neuro-Ophthalmology. - : Informa UK Limited. - 0165-8107 .- 1744-506X. ; 42:2, s. 73-82
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Journal article (peer-reviewed)abstract
- In this study, the authors present a sample of 71 patients with hereditary optic neuropathy and negative genetic test results for OPA1/OPA3/LHON. All of these patients later underwent genetic testing to rule out WFS. As a result, 53 patients (74.7%) were negative and 18 patients (25.3%) were positive for some type of mutation or variation in the WFS gene. The authors believe that this study is interesting because it shows that a sizeable percentage (25.3%) of patients with hereditary optic 25 neuropathy and negative genetic test results for OPA1/OPA3/LHON had WFS mutations or variants.
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| 25. |
- Gálvez-Ruiz, Alberto, et al.
(author)
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Prevalence of diabetic retinopathy in a population of diabetics from the middle east with microvascular ocular motor palsies
- 2016
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In: Journal of Neuro-Ophthalmology. - 1070-8022. ; 36:2, s. 131-133
-
Journal article (peer-reviewed)abstract
- Background: Vascular risk factors are increasing rapidly in the Middle East. Growing inactivity and obesity have contributed to an epidemic of Type 2 diabetes mellitus (DM) in the Arab population. Microvascular palsies of the third, fourth, and sixth cranial nerves, which occur in an isolated manner, are relatively common in patients with DM, hypertension, or other vascular risk factors. Methods: In this retrospective analysis, patients with diabetes with microvascular palsies were assessed for the prevalence of diabetic retinopathy (DR). We compared these data with the prevalence of DR in the general population of diabetics in Saudi Arabia and to a similar published study done in an American population. Results: In total, 126 patients with diabetes were included in the study. The sixth nerve was most frequently involved in 67 patients (53%). Seventy-seven patients (61%) had DR, compared with 49 (39%) without DR. The prevalence of DR in the general population of Saudi patients with diabetes ranged from 30% to 36.1%. Conclusions: Our study demonstrated a higher prevalence of DR in patients with microvascular palsies compared with the general population of patients with diabetes in the Arab population. This is in contrast to a previous study in an American population. Our results might be secondary to differences between the 2 populations, in particular, the continued increase in the prevalence of vascular risk factors (mainly diabetes) and poor control of these risk factors in the Middle East.
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| 26. |
- Galvez-Ruiz, Alberto, et al.
(author)
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Three New PAX2 Gene Mutations in Patients with Papillorenal Syndrome
- 2017
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In: Neuro-Ophthalmology. - : Informa UK Limited. - 0165-8107 .- 1744-506X. ; 41:5, s. 271-278
-
Journal article (peer-reviewed)abstract
- Papillorenal syndrome (PAPRS; Mendelian Inheritance in Man [MIM] 120330) is an autosomal dominant disease characterised by the presence of congenital renal and optic nerve abnormalities associated with mutations of the PAX2 gene. In this article, the authors present four patients with PAPRS who are carriers of three new PAX2 mutations, as well as another patient with a possible non-pathogenic variant of the PAX2 gene. All patients were given a full neurophthalmological examination, and all patients underwent a genetic test for PAX2. Patients 1 and 2 presented with the classic signs of PAPRS: renal disease associated with a congenitally abnormal optic disc, whereas patients 3 and 4 only presented with a congenital optic nerve abnormality and no renal involvement. In patients 1 and 2, the optic nerves were affected by the presence of a central excavation within the optic disc, absence of the central retinal artery, as well as multiple cilioretinal arteries radiating from the periphery of the optic disc. Bilateral optic nerve pits were seen in patient 3, and lastly, in patient 4 there was the presence of superficial gliotic tissue on the left optic disc. All patients presented with a missense mutation in the PAX2 gene, where in patient 4 possibly being only a non-pathogenic variant of the gene. In conclusion, the authors present two patients with classic clinical signs of PAPRS, having two new PAX2 mutations, which until now have not been described in the current literature; another patient with a new PAX2 mutation showing only ocular manifestations of the disease, and lastly, a patient who is a carrier of a variant of the PAX2 gene has a congenitally abnormal optic disc, which is probably not related to PAPRS.
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| 27. |
- Harbi, Majed Al, et al.
(author)
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Association between sickle cell trait and the prevalence and severity of diabetic retinopathy
- 2016
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In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:7
-
Journal article (peer-reviewed)abstract
- Purpose To determine whether Sickle cell trait (SCT) is associated with an increased severity of diabetic retinopathy. Methods This was a single center retrospective study case control study of 100 eyes of 100 patients with diabetes mellitus (DM) with SCT (SCT group) and 100 eyes of 100 age-matched patients with DM without SCT (control group). The main outcome measure was the difference in the prevalence of sight threatening DR [here defined as diabetic macular edema (DME) and/or proliferative diabetic retinopathy (PDR)], between the SCT and control groups. Secondary outcome measures included differences in visual acuity, ocular comorbidities, intraocular pressure, glycemic control as assessed by random blood glucose measurement, diabetes duration, nephropathy, hyperlipidemia and hypertension. Results The SCT group had statistically significantly shorter duration of DM (median [25% quartile] 15 [8.3] years versus 20 [14.7] years, respectively)(P
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| 28. |
- Khan, Arif O., et al.
(author)
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Accommodative esotropia and Brown syndrome in a girl with recessive geleophysic dysplasia
- 2019
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In: JAAPOS. - : Elsevier BV. - 1091-8531. ; 23:2, s. 101-102
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Journal article (peer-reviewed)abstract
- Geleophysic dysplasia and Weill-Marchesani syndrome are acromelic dysplasias characterized by short stature, brachydactyly, and joint contractures. Recessive Weill-Marchesani syndrome typically includes spherophakia, but the ocular phenotype of recessive geleophysic dysplasia is not well defined. We describe the ocular phenotype of a girl with genetically confirmed recessive geleophysic dysplasia (biallelic ADAMTSL2 mutations). Features included high corneal astigmatism, accommodative esotropia, unilateral Brown syndrome, and no evidence for zonular disease at 12 years of age.
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| 29. |
- Kozak, Igor, et al.
(author)
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Teleophthalmology image-based navigated retinal laser therapy for diabetic macular edema : a concept of retinal telephotocoagulation
- 2017
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In: Graefe's Archive for Clinical and Experimental Ophthalmology. - : Springer Science and Business Media LLC. - 0721-832X .- 1435-702X. ; 255:8, s. 1509-1513
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Journal article (peer-reviewed)abstract
- Background: To determine the feasibility and efficacy of a retinal telephotocoagulation treatment plan for diabetic macular edema. Methods: Prospective, interventional cohort study at two clinical sites. Sixteen eyes of ten subjects with diabetic macular edema underwent navigated focal laser photocoagulation using a novel teleretinal treatment plan. Clinic 1 (King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia) collected retinal images and fundus fluorescein angiogram. Clinic 2 (Palmetto Retina Center, West Columbia, SC, USA) created image-based treatment plans based on which macular laser photocoagulation was performed back at clinic 1. The primary outcome of the study was feasibility of image transfer and performing navigated laser photocoagulation for subjects with diabetic macular edema between two distant clinics. Secondary measures were change in best-corrected visual acuity (BCVA) and central retinal thickness (CRT) by spectral-domain optical coherence tomography at 3 months after treatment. Results: The teleretinal treatment plan was able to be successfully completed in all 16 eyes. The mean logMAR BCVA at baseline was 0.49 ± 0.1, which remained stable (0.45 ± 0.1) 3 months after treatment (p = 0.060). The CRT improved from 290.1 ± 37.6 μm at baseline to 270.8 ± 27.7 μm 3 months after treatment (p = 0.005). All eyes demonstrated improvement in the area of retinal edema after laser photocoagulation, and no eyes demonstrated visual acuity loss 3 months after treatment. Conclusion: This study introduces the concept of retinal telephotocoagulation for diabetic macular edema, and demonstrates the feasibility and safety of using telemedicine to perform navigated retinal laser treatments regardless of geographical distance.
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| 30. |
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| 31. |
- Magliyah, Moustafa, et al.
(author)
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Clinical spectrum, genetic associations and management outcomes of Coats-like exudative retinal vasculopathy in autosomal recessive retinitis pigmentosa
- 2021
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In: Ophthalmic Genetics. - : Informa UK Limited. - 1381-6810 .- 1744-5094. ; 42:2, s. 178-185
-
Journal article (peer-reviewed)abstract
- Background: Coats-like retinal vasculopathy in retinitis pigmentosa (RP) is rare. This study describes its clinical spectrum, management outcomes and genetic associations in patients with autosomal recessive RP (arRP). Materials and methods: Retrospective review of ophthalmic, multimodal imaging, genetic findings and treatment outcomes of arRP patients who developed Coats-like features. Identification of patients included searching a retinal dystrophy registry of 798 patients. Results: Ten eyes of six patients with arRP (4 males, 2 females, mean age 33 years) demonstrated Coats-like features, namely inferotemporal peripheral retinal telangiectasis combined with unilateral inferotemporal vasoproliferative tumor (VPT) in 4 eyes. Exudative retinal detachment (ERD) developed in five eyes of which four had VPT. Ablation of the vasculopathy using retinal laser photocoagulation and/or cryotherapy in eight eyes, allowed ERD and/or lipid exudation to decrease in seven eyes despite incomplete vasculopathy regression. Additional intravitreal triamcinolone acetonide injection in one eye failed to regress the ERD and associated VPT. Observation in one eye caused increased exudation. Six mutations, including three novel mutations, were found in CRB1, CNGB1, RPGR, and TULP1. Conclusions: Coats-like features in arRP range from retinal telangiectasis to VPTs with extensive ERD and occur predominantly in the inferotemporal retinal periphery. In addition to their classic association with CRB1 mutations, other genes are implicated. To the best of our knowledge, this is the first report describing CNGB1 mutations in Coats-like RP. Awareness of the vasculopathy spectrum is important, and timely ablation of the vasculopathy with long-term monitoring is recommended to prevent additional visual loss in RP patients.
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| 32. |
- Magliyah, Moustafa, et al.
(author)
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Late presentation of RPE65 retinopathy in three siblings
- 2020
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In: Documenta Ophthalmologica. - : Springer Science and Business Media LLC. - 0012-4486 .- 1573-2622. ; 140:3, s. 289-297
-
Journal article (peer-reviewed)abstract
- Purpose: Gene therapy for RPE65 retinopathy has been recently approved. The purpose of this study was to assess retinal structure and function in 3 siblings presenting with late-stage RPE65 retinopathy and to assess the unmet need for such therapy in Saudi Arabia. Methods: Search of the retinal dystrophy registry at King Khaled Eye Specialist Hospital and clinical examination including multimodal retinal imaging, full-field electroretinography (ERG), dark adapted full-field stimulus sensitivity thresholds, and molecular genetic testing in 3 patients. Results: Nine (9) patients were identified with biallelic RPE65 mutations, corresponding to a prevalence rate of 9/187 = 5% among early onset retinal dystrophies. Of these, 3 siblings (2 male and 1 female) with RPE65 retinopathy were assessed in detail, because of an unusual, late presentation. They were all over 30 years old at the time of their most recent visits and had non-recordable ERGs. The 2 male siblings presented with poor vision and paracentral loss of the inner segment ellipsoid (ISe) and focal attenuation of the outer nuclear layer (ONL) in the macula. On the other hand, the female sibling presented with 20/100 vision with preserved foveal ISe and intact ONL throughout the macula and significantly lower light sensitivity thresholds compared to her male siblings. A homozygous missense p.Arg91Trp mutation in RPE65 was identified in all. All patients were eligible for gene therapy, demonstrating a central retinal thickness of more than 100 microns on repeated examinations. Conclusions: RPE65 retinopathy seems to be relatively common on the Arabian peninsula, and in addition it may be underdiagnosed. To the best of our knowledge, this is the first detailed presentation, including multimodal retinal imaging and electrophysiological assessment, of such patients from this region. Patients with late presentation of RPE65 retinopathy may be eligible for gene therapy, in terms of remaining retinal function and structural preservation. The therapeutic window of such therapy remains to be determined.
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| 33. |
- Magliyah, Moustafa, et al.
(author)
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Manifestation of panuveitis after intraocular surgery in a child with blau syndrome
- 2021
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In: Middle East African Journal of Ophthalmology. - : Medknow. - 0974-9233. ; 28:3, s. 196-198
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Journal article (peer-reviewed)abstract
- Blau syndrome (BS) is a rare granulomatous disease with autosomal dominant inheritance. It is characterized by a triad of dermatitis, arthritis, and recurrent uveitis. This case presents the onset of panuveitis in BS after intraocular surgery. A 10-year-old boy presented to the outpatient clinic with retinal detachment in the left eye after 6 years following early-onset cataract surgery. Bilateral panuveitis occurred 3 weeks after surgical repair and resulted in a total visual loss in the left eye and was persistent to conventional treatment in the right eye. Genetic testing revealed a mutation in NOD2 gene. The addition of adalimumab to the treatment regimen resulted in long-term uveitis control and maintenance of 20/70 vision in the right eye. We propose that NOD2-mediated inflammatory cascade can be activated by intraocular surgery and results in the manifestation of BS.
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| 34. |
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| 35. |
- Magliyah, Moustafa S., et al.
(author)
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Association of the Recurrent Rare Variant c.415T>C p.Phe139Leu in CLN5 with a Recessively Inherited Macular Dystrophy
- 2021
-
In: JAMA Ophthalmology. - : American Medical Association (AMA). - 2168-6165. ; 139:3, s. 339-339
-
Journal article (peer-reviewed)abstract
- Importance: Homozygous variants in the neuronal ceroid lipofuscinosis type 5 (CLN5) gene are associated with neuronal ceroid lipofuscinosis, a progressive neurologic disorder that leads to ataxia, seizures, and early death. The association between a homozygous variant in this gene and a macular dystrophy is described here. Objective: To describe an autosomal recessive macular dystrophy associated with a recurrent variant in CLN5. Design, Setting, and Participants: This cohort study took place at a national referral center and had a follow-up duration ranging between 1 and 5 years. All patients who were identified to carry a specific homozygous missense variant in CLN5, among more than 2000 patients who were diagnosed with or suspected to have retinal dystrophies, who did not carry this variant, were included. Data were collected between June 2014 and September 2020. Exposures: All patients who were sampled for DNA analysis due to molecularly unconfirmed retinal dystrophy and who were subsequently identified to carry the homozygous missense variant c.415T>C (p.Phe139Leu) in CLN5 were included, while patients who did not carry the variant were excluded. Main Outcomes and Measures: Retinal phenotype associated with this specific homozygous missense variant in CLN5. Results: Seven affected patients (mean [SD] age, 43 [18] years; age range, 33-52 years; 5 male) carried the homozygous missense in CLN5. All patients were diagnosed as having a macular dystrophy. Four patients had mild electroretinographic alterations. All patients had hypoautofluorescent maculas with retinal thinning (central subfield thickness, 80 µm). Visual acuity ranged between 2/200 and 20/100. Neurologic symptoms were mild (dizziness) in 5 patients and absent in 2 patients. Neuroimaging demonstrated cerebellar atrophy and white matter lesions, respectively, in 2 patients. Conclusions and Relevance: These results suggest that CLN5, similar to CLN7, may be associated with isolated macular dystrophy as well as neuronal ceroid lipofuscinosis. The variant c.415T>C p.Phe139Leu does not seem to be associated with any prominent neurologic disease at least until the fourth to sixth decades of life. These findings may imply a specific role of CLN5 in macular neurons. Additional study is suggested, such as molecular screening for this variant in cohorts of patients with undiagnosed macular dystrophies and biological studies of its molecular effects..
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| 36. |
- Magliyah, Moustafa S., et al.
(author)
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Evolution of macular hole in enhanced S-cone syndrome
- 2021
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In: Documenta Ophthalmologica. - : Springer Science and Business Media LLC. - 0012-4486 .- 1573-2622. ; 142:2, s. 239-245
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Journal article (peer-reviewed)abstract
- Purpose: To describe the stages of development and natural course of a full-thickness macular hole (FTMH) in a patient with enhanced S-cone syndrome (ESCS). Methods: This study reported the serial ophthalmologic examinations and macular spectral-domain optical coherence tomography (SD-OCT) imaging over a period of 6 years in a 29-year-old man with ESCS confirmed by electroretinography (ERG) and NR2E3 molecular genetic analysis. Results: At presentation, patient had night blindness and visual acuity (VA) of 20/300 in the right eye (OD) and 20/100 in the left eye (OS). Examination showed bilateral retinal midperipheral pigmentary deposits and a macular schisis in OD. Electroretinography and NR2E3 genetic analysis confirmed ESCS. A year later, a lamellar MH (LMH) appeared at the fovea in OD. SD-OCT confirmed it as inner retinal layer LMH with outer retinal preservation and displayed, on the temporal side of the LMH, prominent splitting between the inner and outer retinal layers. At 2 years, a focal defect in the ellipsoid zone appeared on SD-OCT, followed by split in the outer retinal layer creating a progressively expanding outer LMH. The latter had rolled edges which then fused with the inner LMH margins creating a single full-thickness FTMH. Over the next 4 years, enlargement of the FTMH with increased adjacent retinal splitting continued. No visible vitreous abnormalities or vitreoretinal traction forces were identified at any stage during follow-up. VA OD remained unchanged. Conclusion: This case illustrates that the clinical evolution of FTMH in ESCS may be progressive and likely involves degeneration and intraretinal, rather than vitreoretinal, traction. This should be kept in mind when considering surgical intervention in these cases.
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| 37. |
- Magliyah, Moustafa S., et al.
(author)
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Leprel1-related Giant Retinal Tear Detachments Mimic the Phenotype of Ocular Stickler Syndrome
- 2023
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In: Retina. - 0275-004X. ; 43:3, s. 498-505
-
Journal article (peer-reviewed)abstract
- Purpose:To describe the features of retinal detachments and high myopia in patients with novel pathogenic variants in LEPREL1 and report a possible association with nephropathy.Methods:Retrospective study of 10 children with biallelic LEPREL1 pathogenic variants. Data included ophthalmic features, surgical interventions, and genetic and laboratory findings.Results:10 patients (8 females) from three families with homozygous (2) or compound heterozygous (1) variants in LEPREL1 were included. At presentation, mean age was 9.9 ± 2.6 years. Mean axial length was 28.9 ± 1.9 mm and mean refraction was -13.9 ± 2.8 diopters. Bilateral posterior subcapsular cataracts were present in eight patients (80%), with lens subluxation in five eyes of three patients (30%). Rhegmatogenous retinal detachments (RRD), associated with giant retinal tears (GRT), developed in seven eyes of five patients (50%) at a mean age of 14.14 ± 5.9 years. Six were successfully reattached with mean Snellen best-corrected visual acuity improving from 20/120 preoperatively to 20/60 at last follow-up. Urinalysis in nine patients revealed microhematuria and/or mild proteinuria in six patients (67%).Conclusion:LEPREL1-related high myopia confers a high risk of early-onset GRT-related RRD. The ocular phenotype may be confused with that of ocular Stickler syndrome if genetic testing is not performed. Further investigations into a potential association with renal dysfunction are warranted.
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| 38. |
- Magliyah, Moustafa S., et al.
(author)
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Rhegmatogenous Retinal Detachment in Nonsyndromic High Myopia Associated with Recessive Mutations in LRPAP1
- 2020
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In: Ophthalmology Retina. - : Elsevier BV. - 2468-6530. ; 4:1, s. 77-83
-
Conference paper (peer-reviewed)abstract
- Purpose: To describe a new form of childhood-onset rhegmatogenous retinal detachment (RRD) in autosomal recessive high myopia associated with mutations in LRPAP1. Design: Retrospective cohort study. Participants: A total of 12 children (24 eyes) with recessive LRPAP1 mutations and associated high myopia. Methods: Serial ophthalmological examination and retinal imaging during 4.6±1.9 (mean ± standard deviation) years. Retinal interventions included prophylactic laser and surgical retinal repair. Main Outcome Measures: Incidence and recurrence rate of RRD and retinal break formation. Association between LRPAP1 genotypes and RRD characteristics. Results: Some 42% of children (5 children [6 eyes]) developed RRD at the age of 10.43±0.97 years. Four of the children who developed RRD were male (80%), and 1 was female (20%). Visual acuity was significantly reduced in eyes with RRD at presentation and at the most recent visit compared with eyes with no RRD (P < 0.001 for both). Two eyes had inoperable RRD. Four eyes for which primary retinal repair was done had redetachment (100% of operated eyes) due to variable degrees of proliferative vitreoretinopathy (PVR). Reattachment after surgical repair, which was maintained at least during 6 months of follow-up, was achieved in 3 eyes (75%), with final visual acuities of 20/300 in 2 eyes and 20/400 in 1 eye. Conclusions: This is the first description of a nonsyndromic, high myopia-related, recessive RRD without any signs of vitreoretinal degeneration. Recessive LRPAP1 gene mutations confer a high risk of childhood-onset RRD and PVR. Proliferative vitreoretinopathy in turn increases the risk of recurrent RRD and may lead to blindness. Recognizing the LRPAP1-related high myopia phenotype is important, and early childhood examination with additional close follow-up and prophylactic retinal laser should be considered.
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| 39. |
- Milibari, Doaa, et al.
(author)
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Unilateral Retinitis Pigmentosa Associated with Possible Ciliopathy and a Novel Mutation
- 2022
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In: Clinics and Practice. - : MDPI AG. - 2039-7283. ; 12:4, s. 491-500
-
Journal article (peer-reviewed)abstract
- Unilateral retinitis pigmentosa (URP) is a rare retinal dystrophy. We describe the clinical course of two patients with (URP) unilateral retinitis pigmentosa confirmed by genetic testing, indicating ciliary dysfunction. Methods: The methods used in this study included a detailed ophthalmic examination, multimodal retinal imaging, Goldmann visual fields, full-field electroretinography (ffERG) and targeted next-generation sequencing. Results: A 32-year-old female (patient 1) and 65-year-old male (patient 2) were found to have URP. ffERG showed a non-recordable response in the affected eye and a response within normal limits in the fellow eye of patient 1, while patient 2 showed non-recordable responses in the apparently unaffected eye and a profound reduction in the photopic and scotopic responses in the affected eye. Next-generation sequencing revealed novel compound heterozygous c.373 C>T (p.Arg125Trp) and c.730-22_730-19dup variants in AGBL5 in patient 1, and a novel hemizygous c.1286 C>T (p.Pro429Leu) in patient 2; both gene mutations were 0%. Segregation analysis was not possible for either of the mutations. Conclusion: This report expands the clinical and molecular genetic spectrum of URP.
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| 40. |
- Nowilaty, Sawsan R., et al.
(author)
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Incidence and Natural History of Retinochoroidal Neovascularization in Enhanced S-Cone Syndrome
- 2021
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In: American Journal of Ophthalmology. - : Elsevier BV. - 0002-9394. ; 222, s. 174-184
-
Journal article (peer-reviewed)abstract
- Objective: We examined the incidence and natural history of macular retinochoroidal neovascularization (RCN) in enhanced S-cone syndrome (ESCS). Design: Retrospective case series. Methods: This single-center study included 14 of 93 patients with ESCS who had signs of active or inactive RCN in ≥1 eye. We conducted multimodal retinal imaging, full-field electroretinography, and molecular genetic analysis of NR2E3 gene. Our main outcome measures included the cumulative incidence of RCN in ESCS, type of RCN, and mode of evolution of RCN. Results: Fourteen (15.1%) of 93 patients with ESCS had RCN in ≥1 eye at 2 to 27 years of age. All 22 RCNs (21 eyes of 14 patients) were macular. Twelve of the RCNs were active with exudates/hemorrhages. Of these, 5 appeared de novo in a subretinal location, with photographic evidence of no pre-existing lesions. The latter were compatible with type 3 neovascularization or retinal angiomatous proliferation and subsequently evolved into unifocal fibrotic nodules. The remaining active lesions all had some degree of pre-existing fibrosis and remained stable. Ten inactive fibrotic nodules, identical to end-stage de novo lesions, were found and were presumed to represent healed RCNs. Conclusions: RCN, a treatable condition, may occur as early as 2 years of age and may be much more common in patients with ESCS than previously estimated. It may be the primary cause of the unifocal submacular fibrosis that is commonly observed in this condition. Additional research is needed to establish the pathogenesis of RCN in patients with ESCS and its optimal management.
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| 41. |
- Pineiro-Gallego, Teresa, et al.
(author)
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Clinical evaluation of two consanguineous families with homozygous mutations in BEST1
- 2011
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In: Molecular Vision. - 1090-0535. ; 17:179, s. 1607-1617
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Journal article (peer-reviewed)abstract
- Purpose: To describe the clinical and genetic findings in two consanguineous families with Best vitelliform macular dystrophy (BVMD) and homozygous mutations in the bestrophin-1 (BEST1) gene. Methods: Ophthalmologic examination was performed in eight members of two families originating from Spain and Denmark. Mutation screening was performed using the Vitelliform Macular Dystrophy mutation array from Asper Biotech, and by the directed genomic sequencing of BEST1. Results: Two homozygous mutations were detected in these families. Mutation c.936C>A (p.Asp312Glu) has been reported previously in a Danish family; here, we describe four additional individuals in this family demonstrating findings compatible with a severe dominant BVMD, albeit with reduced penetrance in heterozygotes. In the Spanish family, a novel homozygous missense mutation in exon 4, c. 388 C>A (p.Arg130Ser), was identified in the siblings. Homozygous siblings demonstrated evidence of multifocal vitelliform retinopathy, whereas heterozygous family members presented findings ranging from isolated reduction of the electrooculogram Arden ratio to normal values on all clinical parameters. Conclusions: As demonstrated in these consanguineous families, a great clinical variability is associated with homozygous mutations in BEST1, ranging from severe dominant BVMD with reduced penetrance in heterozygotes to autosomal recessive bestrophinopathy.
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| 42. |
- Schatz, Patrik, et al.
(author)
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A tapetal-like fundus reflex in a healthy male: evidence against a role in the pathophysiology of retinal degeneration?
- 2012
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In: Molecular Vision. - 1090-0535. ; 18:119-20, s. 1147-1155
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Journal article (peer-reviewed)abstract
- Purpose: To report on the retinal function and structure in a 37-year-old male who presented with a tapetal-like reflex (TLR) indistinguishable from that seen in female carriers of X-linked retinitis pigmentosa (XLRP). Methods: Clinical examination included dark adaptometry, full-field electroretinography (ERG), multifocal ERG, optical coherence tomography, and fundus autofluorescence photography. Molecular genetic testing included screening for known mutations in autosomal dominant, autosomal recessive, and X linked retinitis pigmentosa (RP) genes with a commercially available chip, and sequencing analysis of retinitis pigmentosa GTPase regulator (RPGR)-open reading frame 15 (ORF15). Results: Fundus examination revealed a bilateral TLR, which is typical of female carriers of XLRP. Imaging studies and electrophysiological testing was unremarkable, except for a significant increase in full-field ERG amplitudes after prolonged dark adaptation as compared to after standard dark adaptation. Mutation screening was negative. Conclusions: TLR was found for the first time, to the best of our knowledge, in a male subject. There were no definitive signs of retinal degeneration, suggesting that this reflex in itself is not necessarily a precursor of the retinal degeneration that can be seen in female carriers of XLRP.
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| 43. |
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| 44. |
- Schatz, Patrik
(author)
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Electrophysiology and optical coherence tomography in acquired and hereditary retinal disorders
- 2006
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Doctoral thesis (other academic/artistic)abstract
- In this thesis, retinal function in general, as well as central retinal function and structure are described in selected forms of acquired and hereditary retinal disorders, in order to improve our understanding of underlying pathogenic mechanisms. This comparison has been made possible during the last years, through the relatively recent development of multifocal ERG (mfERG) and optical coherence tomography (OCT) for the analysis of central retinal function and structure, respectively. The following disorders were investigated: Patients with different mutation in the RDS gene: Phenotypic expression in terms of central retinal structure and function, by OCT and mfERG varied widely, even with the same heterozygous mutation in RDS. Structural alterations were found with OCT in the outer retina choroid complex (ORCC) in a patient with adult onset vitelliform macular degeneration, but function was relatively preserved by mfERG. Patients from a family with autosomal dominant retinitis pigmentosa and a mutation in IMPDH1: Disease expression was homogenous; central retinal function seemed to decrease with age as judged by mfERG, whereas retinal edema seen with OCT, was more pronounced in young patients. Patients with Best macular dystrophy (BMD) and mutation in VMD2: If any functional impairment, the typical appearance in BMD associated with mutations in VMD2, is that of central retinal dysfunction by mfERG and variable structural alterations with OCT. However even in the presence of structural alterations including a lesion in the ORCC, central retinal function may be preserved. Signs of widespread retinopthy were identified in certain genotypes, most noticeably in patients with specific compound heterozygous mutations in VMD2. Patients with recent onset rhegmatogenous retinal detachment (RRD) and solar retinopathy: Central retinal function improves after successful surgery in RRD, or after expectancy in solar retinopahy. Structural alterations in the fovea may be seen, even after successful surgery for RRD. The significance of these in the possible contribution to functional impairment remains to be established. Factors that might influence the outcome include the duration and extent of detachment, and the type of surgery applied.
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| 45. |
- Schatz, Patrik, et al.
(author)
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Evaluation of Macular Structure and Function by OCT and Electrophysiology in Patients with Vitelliform Macular Dystrophy Due to Mutations in BEST1
- 2010
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In: Investigative Ophthalmology & Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 1552-5783 .- 0146-0404. ; 51:9, s. 4754-4765
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Journal article (peer-reviewed)abstract
- PURPOSE. To analyze retinal structure and function in vitelliform macular dystrophy (VMD) due to mutations in BEST1. METHODS. Patients from five Swedish and four Danish families were examined with electrooculography (EOG), full-field electroretinography (ffERG), multifocal ERG (mfERG), optical coherence tomography (OCT), and fundus autofluorescence photography (FAF). Genetic analysis of the BEST1 gene was performed by direct sequencing. RESULTS. Mutations in BEST1 have been reported previously in the Swedish families. In the Danish families, four disease-causing missense mutations were found, one of which is novel: c.936C>A (p.Asp312Glu). The mutation was homozygous in a 9-year-old boy and heterozygous in his father in a consanguineous family. ffERG rod response was reduced in the homozygous boy, but normal in the heterozygous father. EOG was reduced in all but two patients and did not correlate with the ffERG results. OCT ranged from normal to cystoid edema and thickening of the outer retina-choroid complex. Decreased mfERG amplitudes, increased mfERG latencies, and loss of integrity of the foveal photoreceptor inner/outer segment junction, correlated with decreased vision. FAF demonstrated hyperautofluorescence beyond the ophthalmoscopic changes in several patients. CONCLUSIONS. The finding of a homozygous dominant mutation in a patient with VMD and evidence of widespread retinal degeneration may imply that the pathogenesis of the generalized retinal degeneration differs from that of the macular degeneration. A relative agreement between hyperautofluorescence by FAF, reduced retinal function, and VMD implies that the hyperautofluorescence emanates from lipofuscin and A2E. A potential therapy for VMD, involving the inhibition of the retinoid cycle, is suggested. (Invest Ophthalmol Vis Sci. 2010;51:4754 - 4765) DOI:10.1167/iovs.10-5152
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| 46. |
- Schatz, Patrik, et al.
(author)
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Fundus Albipunctatus Associated with Compound Heterozygous Mutations in RPE65.
- 2011
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In: Ophthalmology. - : Elsevier BV. - 1549-4713 .- 0161-6420. ; 118, s. 888-894
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Journal article (peer-reviewed)abstract
- PURPOSE:: To describe a family with an 18-year-old woman with fundus albipunctatus and compound heterozygous mutations in RPE65 whose unaffected parents and 1 female sibling harbored single heterozygous RPE65 mutations. DESIGN:: Observational study. PARTICIPANTS:: Four family members. METHODS:: Clinical examinations included full-field electroretinogram (ffERG) after standard (30-minute) and prolonged (17-hour) dark adaptation, multifocal electroretinogram (mfERG), optical coherence tomography (OCT), and fundus autofluorescence (FAF). Molecular genetic testing included sequencing of RDH5 and RLBP1 and screening for known autosomal-recessive retinitis pigmentosa mutations by a commercially available microarray technique. RPE65 sequencing was performed after the identification of a known heterozygous splice-site mutation by array screening. MAIN OUTCOME MEASURES:: We recorded ffERG and mfERG amplitudes, OCT characteristics, the FAF intensity index, and the outcomes of DNA sequencing regarding RPE65 mutations. RESULTS:: Uniform, yellow-white dots typical of fundus albipunctatus were demonstrated in the proband. These dots corresponded with discrete, hyperreflective formations extending from the Bruch's membrane and retinal pigment epithelium (RPE) into the level of the external limiting membrane, thus spanning along the entire RPE and photoreceptor outer and inner segments. A reduced thickness of the central retina and the RPE-outer segment complex was demonstrated. The intensity of the FAF was severely reduced in the entire fundus. At age 18, ffERG-including prolonged dark adaptation-demonstrated a barely recordable rod response after standard dark adaptation and normalization (increase by more than 700%) of the response after prolonged dark adaptation. The cone 30-Hz flicker response was reduced after standard dark adaptation and increased by >50% after prolonged dark adaptation. In addition, mfERG demonstrated reduced central and peripheral responses. Molecular genetic analysis demonstrated compound heterozygous mutations (IVS1+5G>A and c.344T>C) in RPE65. No mutations were found in RDH5 or RLBP1. No significant abnormalities of retinal structure or function were detected in the parents and sister carrying single heterozygous mutations in RPE65. CONCLUSIONS:: This is the first reported association between compound heterozygous RPE65 mutations and fundus albipunctatus, indicative of a mutation-specific phenotypic effect in this gene. This finding, together with the reduced FAF, supports that disruption of retinoid recycling in the RPE is essential for the development of fundus albipunctatus. FINANCIAL DISCLOSURE(S):: The authors have no proprietary or commercial interest in any of the materials discussed in this article.
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| 47. |
- Schatz, Patrik, et al.
(author)
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LACK OF AUTOFLUORESCENCE IN FUNDUS ALBIPUNCTATUS ASSOCIATED WITH MUTATIONS IN RDH5.
- 2010
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In: Retina. - 1539-2864. ; Okt, s. 1704-1713
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Journal article (peer-reviewed)abstract
- PURPOSE:: The purpose of this study was to characterize the phenotype of fundus albipunctatus associated with RDH5 mutations. METHODS:: Four unrelated patients (patients 1-4) aged 35, 32, 19, and 8 years were examined with full-field electroretinography, multifocal electroretinography, optical coherence tomography, and fundus autofluorescence photography. Molecular genetic investigations included sequencing of RDH5 and RLBP1. RESULTS:: Patients 1 to 3 harbored homozygous mutations (c.881G>C, c.625C>T, and c.382G>A, respectively) and patient 4 harbored the compound heterozygous mutations (c.95delT and c.712G>T) in RDH5. A large variability in retinal dysfunction caused by RDH5 mutations was found but not fully explained by a simple prediction of reduced enzymatic function. All patients showed lack of autofluorescence of the fundus, indicating a reduced supply of 11-cis retinal to the photoreceptors. The lesions corresponding to the white dots did not autofluoresce and were seen on optical coherence tomography as discrete hyperreflective elements in the outer retina extending from the external limiting membrane to Bruch membrane. CONCLUSION:: Mutations in RDH5 associated with fundus albipunctatus seem to prevent normal lipofuscin accumulation. A relatively good functional status of 2 of 3 adult patients indicates that interference with 11-cis retinol dehydrogenase function may be a promising strategy for therapeutic intervention in retinal disorders featuring excessive lipofuscin accumulation.
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| 48. |
- Schatz, Patrik, et al.
(author)
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Macular appearance by means of OCT and electrophysiology in members of two families with different mutations in RDS (the peripherin/RDS gene).
- 2003
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In: Acta Ophthalmologica Scandinavica. - : Wiley. - 1395-3907. ; 81:5, s. 500-507
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Journal article (peer-reviewed)abstract
- Purpose: To describe the phenotype using electroretinography and optical coherence tomography (OCT) in members of two families with different mutations in RDS. Methods: DNA was extracted from blood samples and used for mutation screening by denaturing gradient gel electrophoresis (DGGE) and nucleotide sequencing of RDS exons. Patients were examined with clinical evaluation, full-field electroretinography (ERG), multifocal electroretinography (mfERG) and OCT. Results: An Arg-46 stop codon conversion and a Ser-125 Leu substitution were found, respectively, in affected members of the two families. Phenotypes included retinitis pigmentosa, central areolar choroidal dystrophy, macular dystrophy and adult vitelliform maculopathy. The vitelliform lesion was clearly delineated on OCT, but mfERG showed preserved function. Optical coherence tomography showed attenuation of retinal reflectivity in two cases. Conclusion: By combining traditional investigations with mfERG and OCT, we were able to obtain a more refined evaluation of contributing macular and generalized retinal dysfunction, respectively, in patients with hereditary retinal disease.
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| 49. |
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| 50. |
- Schatz, Patrik, et al.
(author)
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Multimodal imaging in CABP4-related retinopathy
- 2017
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In: Ophthalmic Genetics. - : Informa UK Limited. - 1381-6810 .- 1744-5094. ; 38:5, s. 459-464
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Journal article (peer-reviewed)abstract
- Purpose: Multimodal imaging has not been documented for CABP4-related retinopathy. In this study, we describe optical coherence tomography (OCT) and fundus autofluorescence findings for five genetically confirmed cases. Methods: Retrospective case series. Results: Four patients with the previously described homozygous Saudi CABP4 founder mutation c.81_82insA (p.Pro28ThrfsX44) and one patient with the homozygous mutation c.1A>G (p.Met1?) in CABP4 were examined. The ages ranged between 9 and 16 years at last follow-up, and the duration of follow-up ranged from 2 to 12 years. Foveal thickness was reduced ranging between 175 and 212 micrometers. Wide field imaging including fundus autofluorescence was unremarkable. All patients presented with a negative electroretinogram, with a variable amount of cone and rod dysfunction. Over follow-up, there was no electroretinographic indication of any progressive retinal dysfunction. Conclusions: Foveal thinning is a feature of CABP4 retinopathy. Normal autofluorescence is consistent with inner retinal dysfunction and suggests the condition could be amenable to gene therapy. Retinal dysfunction was stable throughout follow-up.
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