Real-world outcomes of voretigene neparvovec treatment in pediatric patients with RPE65-associated Leber congenital amaurosis.

PURPOSE: To investigate real-world safety and efficacy of voretigene neparvovec gene therapy administration in pediatric patients with biallelic RPE65 disease-causing variants. METHODS: A retrospective study of 27 eyes of 14 patients with RPE65-associated Leber congenital amaurosis examined postoperative complications and longitudinal changes in photoreceptor function following treatment with subretinal injection of voretigene neparvovec. Full-field stimulus threshold testing (FST), Goldmann visual fields (GVF), best-corrected visual acuity (BCVA), and central subfield thickness (CST) on optical coherence tomography (OCT) scans were collected preoperatively and up to 12 months posttreatment. RESULTS: Baseline through 6-12 month follow-up FST and GVF data were obtained for 13 eyes of 7 patients. FST improved for each eye after treatment with a mean improvement of 2.1 log-units (P < 0.001) and GVF improved for each eye with a mean improvement of 221 sum degrees (P < 0.001). BCVA improved from logMAR 0.98 at baseline to logMAR 0.83 at last follow-up (P < 0.001). Across 19 eyes of 10 patients included in CST analysis, there was a small but statistically significant 9-µ decrease in mean CST from baseline to last follow-up (P < 0.001). The most common postoperative issues included elevation in intraocular pressure (59%), persistent intraocular inflammation (15%), and vitreous opacities (26%) that resolved over a period of months. CONCLUSIONS: This report provides some of the earliest longitudinal real-world evidence of the pediatric safety and efficacy of voretigene neparvovec using multiple functional and structural measures of the retina. Outcomes demonstrate significant improvements in visual function consistent with clinical trial results.

Contrast sensitivity deficits in patients with mutation-proven inherited retinal degenerations.

BACKGROUND: Patients with retinal diseases frequently complain of poor visual function even when visual acuity is relatively unaffected. This clinical finding has been attributed to deficits in contrast sensitivity (CS). The purpose of our study was to evaluate the CS in patients with clinical and genetic diagnosis of inherited retinal degeneration (IRD) and relatively preserved visual acuity. METHODS: Seventeen patients (30 eyes) with IRD and visual acuity of 20/40 or better, and 18 controls (18 eyes) without any ocular condition underwent slit lamp examination, visual acuity testing via standard Snellen chart testing, CS testing via the Quick Contrast Sensitivity Function (QCSF), and Spectral Domain Optical Coherence Tomography (SD-OCT). CS were measured at 1.0, 1.5, 3.0, 6.0, 12.0, and 18.0 cycles per degree (cpd). T tests with general estimated equations were used to compare CS between groups. Wald chi square followed by pairwise comparisons was used to compare CS between multiple groups. RESULTS: We included 12 patients with rod-cone dystrophy (RCD), 3 patients with Stargardt disease (STGD) and 2 patients with Best disease. Patients with IRD had significantly worse CS than controls (p < 0.001) in all spatial frequencies. Patients with STGD had more marked deficits in CS than patients with Best disease (p < 0.001) and RCD (p < 0.001) despite having similar visual acuities. CONCLUSION: Patients with IRD, especially patients with STGD with relatively preserved visual acuity have marked deficits in CS when measured across a range of spatial frequencies. We recommend that clinical trials for STGD incorporate CS measured over a range of spatial frequencies as a secondary clinical endpoint for monitoring visual function. CS may provide an explanation for complaints of visual dysfunction when visual acuity is not significantly altered.

Optical Coherence Tomography Examination of the Retinal Pigment Epithelium in Best Vitelliform Macular Dystrophy.

PURPOSE: To describe the anatomic changes and natural history of vitelliform lesions in Best vitelliform macular dystrophy (BVMD) using spectral-domain optical coherence tomography (OCT). DESIGN: Prospective comparative case series. PARTICIPANTS: Twenty patients (40 eyes) with molecular confirmation of mutation in the BEST1 gene and 20 age-matched controls were included. METHODS: Color fundus photographs, fundus autofluorescence, and spectral-domain OCT were obtained, and these findings were compared between the 2 groups. Fifteen of the 20 patients with Best disease had more than 1 visit, and the imaging studies from each visit were compared with each other over time. MAIN OUTCOME MEASURES: Evolution of visual acuity and clinical stage of BVMD correlated to OCT measurement parameters, including retinal pigment epithelium (RPE) thickness, central macular thickness, and integrity of the ellipsoid zone. RESULTS: Patients with BVMD demonstrated progressive disorganization and thinning of the submacular RPE on OCT when compared with normal controls. Concurrent with the appearance of "egg-yolk lesions," the OCT showed a cleft in the outer retina, creating an apical and basal separation of retinal layers. The apical complex of the vitelliform lesion eventually degenerated and flattened. Patients with such lesions nevertheless maintained reasonable visual acuity into the advanced vitelleruptive stages despite the disruption of normal anatomic changes. CONCLUSIONS: Our study suggests that in BVMD, subretinal vitelliform material accumulation leads to a clear separation of the outer retinal layers. The level at which this cleft forms is a topic of discussion and interest, with the most likely levels of least resistance being the interdigitation zone or between the RPE and the Bruch's membrane. It is possible that RPE may continue to form a preserved photoreceptor-RPE complex that provides essential nutrients to the photoreceptors and in turn helps patients maintain better than expected visual acuity for years.

Digital quantification of Goldmann visual fields (GVFs) as a means for genotype-phenotype comparisons and detection of progression in retinal degenerations.

PURPOSE: To develop a reliable and efficient digital method to quantify planimetric Goldmann visual field (GVF) data to monitor disease course and treatment responses in retinal degenerative diseases. METHODS: A novel method to digitally quantify GVFs using Adobe Photoshop CS3 was developed for comparison to traditional digital planimetry (Placom 45C digital planimeter; Engineer Supply, Lynchburg, Virginia, USA). GVFs from 20 eyes from 10 patients with Stargardt disease were quantified to assess the difference between the two methods (a total of 230 measurements per method). This quantification approach was also applied to 13 patients with X-linked retinitis pigmentosa (XLRP) with mutations in RPGR. RESULTS: Overall, measurements using Adobe Photoshop were more rapidly performed than those using conventional planimetry. Photoshop measurements also exhibited less inter- and intraobserver variability. GVF areas for the I4e isopter in patients with the same mutation in RPGR who were nearby in age had similar qualitative and quantitative areas. CONCLUSIONS: Quantification of GVFs using Adobe Photoshop is quicker, more reliable, and less user dependent than conventional digital planimetry. It will be a useful tool for both retrospective and prospective studies of disease course as well as for monitoring treatment response in clinical trials for retinal degenerative diseases.

Twelve-month Natural History Study of Centrosomal Protein 290 (CEP290)-associated Inherited Retinal Degeneration.

Purpose: To define the clinical characteristics of centrosomal protein 290 (CEP290)-associated inherited retinal degeneration (IRD) and determine which assessments may provide reliable endpoints in future interventional trials. Design: Participants in this natural history study were enrolled into 2 best-corrected visual acuity (BCVA) cohorts: light perception to > 1.0 logarithm of the minimum angle of resolution (logMAR) and 1.0 logMAR to 0.4 logMAR. Each comprised 4 age cohorts (3-5, 6-11, 12-17, and ≥ 18 years). Participants: Patients with CEP290-associated IRD caused by the intron 26 c.2991+1655A>G mutation and BCVA ranging from light perception to 0.4 logMAR. Methods: Best-corrected visual acuity, full-field stimulus threshold (FST) sensitivity, Ora-Visual Navigation Challenge (Ora-VNC) composite score, and OCT-outer nuclear layer (OCT-ONL) average thickness were assessed at screening, baseline, 3 months, 6 months, and 12 months. Main Outcome Measures: Best-corrected visual acuity, FST sensitivity, Ora-VNC composite score, and OCT-ONL average thickness. Results: Twenty-six participants were included in this analysis. Nineteen were female. All participants were White and 4 reported Hispanic ethnicity. At screening, 13 of 16 adult and 9 of 10 pediatric participants had BCVA > 1.0 logMAR. Baseline BCVA was variable (median [range] = 2.0 [0.5, 3.9] logMAR) and was uncorrelated with age, as were VNC composite score, FST sensitivity, and OCT-ONL average thickness. Mean (95% confidence interval [CI]) test-retest variability was -0.04 (-0.09, 0.01) logMAR for BCVA (n = 25); 0.6 (-0.1, 1.3) for VNC composite score (n = 18); and 0.10 (-0.07, 0.27) log cd.s/m2 for red FST (n = 14). A greater than expected test-retest variability (5 [0, 10] µm, n = 14) was observed for OCT-ONL average thickness as nystagmus impacted ability to repeat measures at the same retinal location. Functional assessments were stable over 12 months. Mean (95% CI) change from baseline was 0.06 (-0.17, 0.29) logMAR for BCVA (n = 23); -0.1 (-1.2, 1.0) for VNC composite score (n = 21); and -0.15 (-0.43, 0.14) log cd.s/m2 for red FST (n = 16). Conclusions: Vision was stable over 12 months. Best-corrected visual acuity, FST, and VNC composite score are potentially viable endpoints for future studies in CEP290-associated IRD. Repeatability of OCT measures poses challenges for quantifying anatomical changes in this population. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Beyond the NEI-VFQ: Recent Experience in the Development and Utilization of Patient-Reported Outcomes for Inherited Retinal Diseases.

Patient-reported outcome measures (PROMs) are tools designed to capture how a patient feels or functions, without the input or interpretation of anyone else. The earliest PROMs used in studies of inherited retinal diseases (IRDs) lack the validity required for therapy development today. The NEI-VFQ was one of the earliest PROMs developed using concept elicitation and cognitive debriefing of patients, but it lacks items that are common to patients with IRDs and it has poor measurement properties. Recent advances in PROM development include the Michigan Retinal Degeneration Questionnaire (MRDQ) and the ViSIO-PRO for nonsyndromic retinitis pigmentosa (RP), both of which have been qualitatively and quantitatively validated. As these new tools are used in clinical studies, they will generate additional evidence about their measurement characteristics. With the latest advances in PROM development for IRDs, it is now possible to move beyond the NEI-VFQ to measure what is truly important to patients.

SUCCESSFUL SURGICAL TREATMENT OF MACULA-INVOLVING DEGENERATIVE RETINOSCHISIS BY VITRECTOMY AND DRAINAGE OF THE SCHISIS CAVITY.

PURPOSE: To demonstrate the potential for visual recovery after surgery for early foveal involvement by progressive degenerative retinoschisis. METHODS: Surgical case report. RESULTS: A 79-year-old woman was monitored over 4 years for degenerative retinoschisis in the inferotemporal periphery of both eyes. Over the course of follow-up, visual acuity in the left eye decreased from 20/40 to 20/100, concurrent with extension of the schisis cavity into the macula. Macular involvement was confirmed on optical coherence tomography imaging, and there was no rhegmatogenous retinal detachment. The patient elected to undergo 25-gauge pars plana vitrectomy and drainage of the schisis cavity. Eleven weeks after surgery, the macula remained attached, and the uncorrected visual acuity was 20/30. Fundus examination and spectral domain optical coherence tomography confirmed ongoing resolution of the macula-involving retinoschisis. CONCLUSION: Bullous degenerative retinoschisis is believed to result in an absolute scotoma that is not surgically correctable. Our patient's excellent visual recovery suggests that the synaptic integrity of the macular outer plexiform layer can be preserved and a permanent scotoma avoided if early macular involvement by progressive degenerative retinoschisis is surgically repaired.

Intravitreal Delivery of rAAV2tYF-CB-hRS1 Vector for Gene Augmentation Therapy in Patients with X-Linked Retinoschisis: 1-Year Clinical Results.

PURPOSE: To evaluate the safety and efficacy of rAAV2tYF-CB-hRS1, a recombinant adeno-associated virus vector expressing retinoschisin (RS1), in individuals with retinal disease caused by mutations in the RS1 gene. DESIGN: Open-label, phase I/II dose-escalation clinical trial. SUBJECTS: Twenty-two adults and 5 children with X-linked retinoschisis (XLRS), aged 10 to 79 years, were enrolled. METHODS: The participants received an intravitreal (IVT) injection of rAAV2tYF-CB-hRS1, at 1 of 3 dose levels, in the poorer-seeing eye and were followed up for a minimum of 1 year after treatment. MAIN OUTCOME MEASURES: The primary safety measures were local (ocular) or systemic (nonocular) adverse events (AEs) during the 12-month period after study agent administration. Efficacy was assessed based on measures of best-corrected visual acuity (BCVA), schisis cavity volume, static perimetry visual field testing, and electroretinography (ERG). RESULTS: The IVT administration of rAAV2tYF-CB-hRS1 was generally safe at each of the dose levels. There were no AEs resulting in early termination, and no dose-limiting toxicities were reported. The most common ocular AEs observed were related to ocular inflammation (blurred vision, visual impairment, and the presence of vitreous cells, keratic precipitates, vitreous floaters, anterior chamber cells, and vitreous haze). Ocular inflammation was generally either mild or moderate in severity and responsive to standard immunosuppressive therapy, except in 3 participants (all in the highest-dose group) who developed chronic uveitis, which required prolonged therapy. Two patients experienced retinal detachments. There was no overall improvement in BCVA, visual fields, or ERG in the study eye compared with that in the fellow eye for any dose group. Variable changes in the cystic cavity volume over time were similar in the study and fellow eyes. CONCLUSIONS: Gene augmentation therapy with rAAV2tYF-CB-hRS1 for XLRS was generally safe and well tolerated but failed to demonstrate a measurable treatment effect. The clinical trial is ongoing through 5 years of follow-up to assess its long-term safety.

Pyramidal Inflammatory Deposits of the Retinal Pigment Epithelium and Outer Retina in Ocular Syphilis.

PURPOSE: To evaluate the role of OCT in the diagnosis of uveitis secondary to syphilis. DESIGN: Consecutive, retrospective case series. PARTICIPANTS: All patients 18 years of age or older with ocular syphilis from 2 tertiary referral centers. METHODS: All patients who were diagnosed with intermediate uveitis, posterior uveitis, or panuveitis secondary to syphilis were included in the study (40 patients representing a total of 62 eyes) to identify important imaging features to aid in diagnosis. Patients underwent confirmatory serologic testing, OCT imaging, and dilated examination by a uveitis specialist. MAIN OUTCOME MEASURE: Hyperreflective retinal lesions on OCT. RESULTS: The mean age of the study population was 42.9 ± 12.16 years. Forty-five percent of the eyes included in this study harbored hyperreflective pyramidal lesions of the outer retina and retinal pigment epithelium on OCT. Fifty-four percent of eyes with these imaging findings did not show a placoid retinal lesion on examination. Sixty-eighty percent of the described outer retinal lesions on OCT resolved after treatment for syphilis. Visual acuity ranged from normal (20/20) to no light perception, with a mean of 20/43 at diagnosis, and improved significantly to a mean visual acuity of 20/26 after treatment (P < 0.05). Vision-threatening complications were seen in less than 5% of eyes and included both treatable and irreversible causes of vision loss, including retinal detachment, cystoid macular edema, and optic neuropathy. CONCLUSIONS: Patients treated for uveitis secondary to syphilis achieve good visual recoveries. Outer retinal lesions seen on OCT are common and can serve as an additional imaging finding of the disease.

Density-based classification in diabetic retinopathy through thickness of retinal layers from optical coherence tomography.

Diabetic retinopathy (DR) is a severe retinal disorder that can lead to vision loss, however, its underlying mechanism has not been fully understood. Previous studies have taken advantage of Optical Coherence Tomography (OCT) and shown that the thickness of individual retinal layers are affected in patients with DR. However, most studies analyzed the thickness by calculating summary statistics from retinal thickness maps of the macula region. This study aims to apply a density function-based statistical framework to the thickness data obtained through OCT, and to compare the predictive power of various retinal layers to assess the severity of DR. We used a prototype data set of 107 subjects which are comprised of 38 non-proliferative DR (NPDR), 28 without DR (NoDR), and 41 controls. Based on the thickness profiles, we constructed novel features which capture the variation in the distribution of the pixel-wise retinal layer thicknesses from OCT. We quantified the predictive power of each of the retinal layers to distinguish between all three pairwise comparisons of the severity in DR (NoDR vs NPDR, controls vs NPDR, and controls vs NoDR). When applied to this preliminary DR data set, our density-based method demonstrated better predictive results compared with simple summary statistics. Furthermore, our results indicate considerable differences in retinal layer structuring based on the severity of DR. We found that: (a) the outer plexiform layer is the most discriminative layer for classifying NoDR vs NPDR; (b) the outer plexiform, inner nuclear and ganglion cell layers are the strongest biomarkers for discriminating controls from NPDR; and (c) the inner nuclear layer distinguishes best between controls and NoDR.

Macular hyperpigmentary changes in ABCA4-Stargardt disease.

BACKGROUND: Stargardt disease (STGD) and age-related macular degeneration (AMD) share clinical and pathophysiological features. In AMD, macular hyperpigmentary changes are associated to a worse prognosis. The purpose of this study was to characterize macular hyperpigmentary changes in patients with STGD and associate them with the severity of phenotype. MATERIALS AND METHODS: This retrospective cross-sectional study included 141 patients with STGD. Hyperpigmentary changes were evaluated on color fundus photography and spectral-domain optical coherence tomography. Severity of phenotype was assessed by full-field electroretinogram (ffERG) and fundus autofluorescence (FAF) patterns, and visual acuity (VA). RESULTS: Thirty patients (21.7%) showed macular hyperpigmentary changes in four distinct patterns. Out of seventeen patients who had follow-up images, eleven patients demonstrated increases of the hyperpigmented lesions, and progression of the underlying RPE atrophy overtime. VA remained stable. Of 28 patients who had ffERG, 17 patients presented with reduction of photopic and scotopic responses, while 8 presented with reduction of photopic responses only, and 3 presented with preserved photopic and scotopic responses. Of 25 patients who had FAF available, 12 presented with widespread disease extending anteriorly to the vascular arcades, while eight presented with widespread disease, extending beyond the vascular arcades, and 5 presented with disease confined to the foveal area. CONCLUSION: In this study, we demonstrated that patients with STGD with macular hyperpigmented lesions had a severe phenotype. Overtime, hyperpigmented lesions increased in size, spread across the retina, and migrated to different retinal layers. Macular hyperpigmentation may be a marker of advanced stage of the disease.

Diurnal variations of foveoschisis by optical coherence tomography in patients with RS1 X-linked juvenile retinoschisis.

BACKGROUND: To evaluate diurnal variations in macular schisis cavities in patients with X-linked juvenile retinoschisis (XLRS) with pathogenic variants in the RS1 gene using spectral-domain optical coherence tomography (SD-OCT). METHODS: Three consecutive patients with a clinical diagnosis of XLRS and pathogenic variants in the RS1, treated with carbonic anhydrase inhibitors (CAIs). Observational procedures: SD-OCT scans of the macula were acquired at 9 a.m., 1 p.m., and 4 p.m. within 24 h. RESULTS: All patients demonstrated increased measures of central foveal thickness in the morning with gradual decrease through the day (9-43%). Major changes were observed between 9 a.m. and 1 p.m. in the central foveal thickness. CONCLUSION: The central foveal thickness varies during daytime hours in patients with XLRS. This finding may explain the inconsistent and heterogeneous responses to treatment with CAIs and necessitate standardization of measurement times in treatment trials for XLRS as well as in the routine ophthalmic evaluation of these patients.

Peripheral Pigmented Retinal Lesions in Stargardt Disease.

PURPOSE: To investigate the prevalence of peripheral pigmented retinal lesions and associated clinical findings in patients with Stargardt disease. DESIGN: Retrospective case series. METHODS: Records at a single academic institution were reviewed for patients with genetically confirmed Stargardt disease with peripheral pigmented retinal lesions on wide-field retinal imaging. For this cohort we described demographics, clinical features, and pathogenic variants. RESULTS: Out of 62 patients with Stargardt disease and wide-field retinal imaging, 14 had peripheral pigmented retinal lesions. These flat, subretinal lesions were located in the mid or far periphery and had well-defined borders, resembling congenital hypertrophy of retinal pigment epithelium (CHRPE) lesions. For this group of 14 patients, median age at initial diagnosis of Stargardt disease was 9.5 years, and the median duration of disease was 21.5 years. Median Snellen visual acuity was 20/200, and median central scotoma size was 20.0 degrees. All 14 patients had electroretinographic abnormalities. Four out of 14 patients developed new lesions during clinical follow-up. CONCLUSIONS: Wide-field retinal imaging revealed the presence of peripheral pigmented retinal lesions resembling CHRPE lesions in a subset of patients with genetically confirmed Stargardt disease. Presence of these lesions may be associated with severe phenotypes of the disease.

Effect of Oral Valproic Acid vs Placebo for Vision Loss in Patients With Autosomal Dominant Retinitis Pigmentosa: A Randomized Phase 2 Multicenter Placebo-Controlled Clinical Trial.

Importance: There are no approved drug treatments for autosomal dominant retinitis pigmentosa, a relentlessly progressive cause of adult and childhood blindness. Objectives: To evaluate the potential efficacy and assess the safety of orally administered valproic acid (VPA) in the treatment of autosomal dominant retinitis pigmentosa. Design, Setting, and Participants: Multicenter, phase 2, prospective, interventional, placebo-controlled, double-masked randomized clinical trial. The study took place in 6 US academic retinal degeneration centers. Individuals with genetically characterized autosomal dominant retinitis pigmentosa were randomly assigned to receive treatment or placebo for 12 months. Analyses were intention-to-treat. Interventions: Oral VPA 500 mg to 1000 mg daily for 12 months or placebo. Main Outcomes and Measures: The primary outcome measure was determined prior to study initiation as the change in visual field area (assessed by the III4e isopter, semiautomated kinetic perimetry) between baseline and month 12. Results: The mean (SD) age of the 90 participants was 50.4 (11.6) years. Forty-four (48.9%) were women, 87 (96.7%) were white, and 79 (87.8%) were non-Hispanic. Seventy-nine participants (87.8%) completed the study (42 [95.5%] received placebo and 37 [80.4%] received VPA). Forty-two (46.7%) had a rhodopsin mutation. Most adverse events were mild, although 7 serious adverse events unrelated to VPA were reported. The difference between the VPA and placebo arms for mean change in the primary outcome was -150.43 degree2 (95% CI, -290.5 to -10.03; P = .035). Conclusions and Relevance: This negative value indicates that the VPA arm had worse outcomes than the placebo group. This study brings to light the key methodological considerations that should be applied to the rigorous evaluation of treatments for these conditions. This study does not provide support for the use of VPA in the treatment of autosomal dominant retinitis pigmentosa. Trial Registration: ClinicalTrials.gov Identifier: NCT01233609.

Cystoid macular changes on optical coherence tomography in a patient with maternally inherited diabetes and deafness (MIDD)-associated macular dystrophy.

The clinical presentation and optical coherence tomography findings in a patient with maternally inherited diabetes and deafness (MIDD) are presented to highlight the presence of macular cystoid spaces in some patients with this disease. Typically, patients with MIDD demonstrate progression of a pigmentary maculopathy into areas of geographic macular atrophy. At the time of initial visit, the 30-year-old patient had large macular cystoid changes in addition to retinal pigmentary changes in both eyes. The cystoid changes responded to treatment with systemic immunosuppression and a topical carbonic anhydrase inhibitor (CAI), recurred when treated with topical CAI monotherapy, and finally resolved after an intravitreal triamcinolone acetonide injection. Over time, the retinal atrophy continued to progress, but the macular cysts did not recur. The patient received systemic immunosuppression for renal transplantation due to renal failure resulting from focal glomerulosclerosis. There was no evidence of diabetic retinopathy at any time during the five-and-a-half-year follow-up, and the patient retained good visual acuity in both eyes.

Peripheral Visual Fields in ABCA4 Stargardt Disease and Correlation With Disease Extent on Ultra-widefield Fundus Autofluorescence.

PURPOSE: To evaluate the disease extent on ultra-widefield fundus autofluorescence (UWF-FAF) in patients with ABCA4 Stargardt disease (STGD) and correlate these data with functional outcome measures. DESIGN: Retrospective cross-sectional study. METHODS: Setting: Kellogg Eye Center, University of Michigan. STUDY POPULATION: Sixty-five patients with clinical diagnosis and proven pathogenic variants in the ABCA4 gene. Observational Procedures: The UWF-FAF images were obtained using Optos (200 degrees) and classified into 3 types. Functional testing included kinetic widefield perimetry, full-field electroretinogram (ffERG), and visual acuity (VA). All results were evaluated with respect to UWF-FAF classification. MAIN OUTCOME MEASURES: Classification of UWF-FAF; area comprising the I4e, III4e, and IV4e isopters; ffERG patterns; and VA. RESULTS: For UWF-FAF, 27 subjects (41.5%) were classified as type I, 17 (26.2%) as type II, and 21 (32.4%) as type III. The area of each isopter correlated inversely with the extent of the disease and all isopters were able to detect differences among UWF-FAF types (IV4e, P = .0013; III4e, P = .0003; I4e, P < .0001 = 3.93e-8). ffERG patterns and VA were also different among the 3 UWF-FAF types (P < .001 = 6.61e-6 and P < .001 = 7.3e-5, respectively). CONCLUSION: Patients with widespread disease presented with more constriction of peripheral visual fields and had more dysfunction on ffERG and worse VA compared to patients with disease confined to the macula. UWF-FAF images may provide information for estimating peripheral and central visual function in STGD.

Prevalence of Antiretinal Antibodies in Acute Zonal Occult Outer Retinopathy: A Comprehensive Review of 25 Cases.

PURPOSE: To perform a comprehensive review and to investigate the presence and role of autoimmune antibodies in 25 cases of acute zonal occult outer retinopathy (AZOOR) identified using the classification originally proposed by J. Donald Gass. DESIGN: Observational case series. METHODS: Setting: Institutional. STUDY POPULATION: Twenty-five patients were identified by characteristic symptoms (abrupt onset of photopsias, followed by large scotomata at or connected to the blind spot), ocular findings (paucity of pigmentary changes with no sign of vitreous inflammation and abnormal electroretinogram in at least 1 eye), and a negative family history for retinitis pigmentosa. OBSERVATION PROCEDURES: Patients underwent a full comprehensive ophthalmologic examination, fundus retinography, Goldmann kinetic visual field (GVF), and full-field electroretinogram (ffERG). Blood samples were also obtained to verify for the presence of antiretinal antibodies by Western blot analysis. MainOutcome Measures: Clinical presentation, best-corrected visual acuity (BCVA), fundus abnormalities, visual field defects, ffERG changes, and presence of antiretinal antibodies. RESULTS: Sixteen patients (64%) presented with photopsias, 56% (14/25) with night blindness, and 56% (14/25) with loss of peripheral vision. Sixty-four percent (16/25) of cases were bilateral. All patients demonstrated retinal vascular attenuation, optic nerve head pallor, and mottling of retinal pigment epithelium. The most common visual field changes included enlargement and expansion of the blind spot extending into large pericentral or other types of scotomata (64%). Both scotopic and photopic ffERG values were abnormal and affected to a similar degree in our patients. Nine patients (36%) had a greater than 20% asymmetry in ERG values between the 2 eyes. All patients had antiretinal antibodies on Western blot with an average of 6.6 bands. CONCLUSION: Evidence suggests that AZOOR is a unique form of autoimmune retinopathy and retinal manifestation suggests possible antiretinal antibody leakage from the disc margin with spread of immune products under the retina, resulting in large scotomata that connect to the optic nerve head.

Regional correlation of structure and function in glaucoma, using the Disc Damage Likelihood Scale, Heidelberg Retina Tomograph, and visual fields.

PURPOSE: To evaluate relationships between the Disc Damage Likelihood Scale (DDLS), global and sectoral structural parameters provided by the Heidelberg Retina Tomograph (HRT), and global and regional functional loss in visual field (VF) testing. DESIGN: Consecutive observational case series. PARTICIPANTS: One hundred ten eyes from 110 patients categorized as glaucoma, glaucoma suspect, or normal. METHODS: Participants were examined clinically to grade the DDLS score and were tested with HRT and Swedish Interactive Threshold Algorithm standard 24-2 VF tests. All tests were performed within 6 months of each other by examiners masked to the other findings. For each patient, the eye with the worse mean deviation (MD) of the VF test was enrolled in the study. Each field was divided into 6 sectors based on a published scheme, and the MD for each sector was calculated. The relationships among clinical DDLS score, HRT parameters, and VF indexes were analyzed by correlation coefficients and linear regression analysis. MAIN OUTCOME MEASURES: The relationship between the DDLS score, global and sectoral optic disc (HRT) parameters, and global and sectoral VF MDs was evaluated. RESULTS: The DDLS showed significant correlation with all global and sectoral VF indexes (r = -0.39 to -0.62, all Ps < 0.0001) and with sectoral rim area HRT measurements (r = -0.27 to -0.51, all Ps < 0.006). The DDLS correlated most strongly with superior and inferior regional data from HRT and VF, and less well with temporal and nasal data. Heidelberg Retina Tomograph rim area and rim volume were the only HRT parameters to correlate moderately with global VF MD (r = 0.30, P = 0.0018, and r = 0.28, P = 0.0030, respectively). Sectoral HRT rim area correlated moderately strongly with the corresponding sectoral VF MDs in the superior and inferior sectors (r = 0.35-0.46, P = <0.0001-0.04). CONCLUSION: Clinical disc assessment and laser tomographic data that determine the state of the neuroretinal rim are associated with sensitivity loss in VF testing in corresponding regions.

Structure/Psychophysical Relationships in X-Linked Retinoschisis.

PURPOSE: To compare structural properties from spectral-domain optical coherence tomography (SDOCT) and psychophysical measures from a subset of patients enrolled in a larger multicenter natural history study of X-linked retinoschisis (XLRS). METHODS: A subset of males (n = 24) participating in a larger natural history study of XLRS underwent high-resolution SDOCT. Total retina (TR) thickness and outer segment (OS) thickness were measured manually. Shape discrimination hyperacuity (SDH) and contour integration perimetry (CIP) were performed on an iPad with the myVisionTrack application. Sensitivity was measured with fundus-guided perimetry (4-2 threshold testing strategy; 10-2 grid, spot size 3, 68 points). Correlation was determined with Pearson's r correlation. Values are presented as the mean ± SD. RESULTS: Mean macular OS thickness was less in XLRS patients (17.2 ± 8.1 µm) than in controls (37.1 ± 5.7 µm; P < 0.0001) but mean TR thickness was comparable (P = 0.5884). For patients, total sensitivity was lower (13.2 ± 6.6 dB) than for controls (24.2 ± 2.4 dB; P = 0.0008) and had a strong correlation with photoreceptor OS (R(2) = 0.55, P = 0.0001) and a weak correlation with TR thickness (R(2) = 0.22, P = 0.0158). The XLRS subjects had a logMAR best corrected visual acuity (BCVA) of 0.5 ± 0.3 that was associated with OS (R(2) = 0.79, P < 0.0001) but not TR thickness (R(2) = 0.01, P = 0.6166). Shape DH and CIP inner ring correlated with OS (R(2) = 0.33, P = 0.0085 and R(2) = 0.47, P = 0.0001, respectively) but not TR thickness (R(2) = 0.0004, P = 0.93; R(2) = 0.0043, P = 0.75, respectively). CONCLUSIONS: When considered from a single visit, OS thickness within the macula is more closely associated with macular function than TR thickness within the macula in patients with XLRS.