Assessment of Visual Function With Cotoretigene Toliparvovec in X-Linked Retinitis Pigmentosa in the Randomized XIRIUS Phase 2/3 Study.

PURPOSE: Cotoretigene toliparvovec (BIIB112/AAV8-RPGR) is an investigational vector-based gene therapy designed to provide a full-length, codon-optimized, retinitis pigmentosa GTPase regulator (RPGR) protein to individuals with RPGR-associated X-linked retinitis pigmentosa (XLRP). We assessed efficacy and safety of cotoretigene toliparvovec subretinal gene therapy. DESIGN: Part 2 of the XIRIUS trial (NCT03116113) was a Phase 2/3, 12-month, randomized (1:1:1), dose-expansion study. PARTICIPANTS: Males aged ≥10 years with RPGR-associated XLRP were included. METHODS: Participants were randomized 1:1:1 to subretinal cotoretigene toliparvovec low dose (5 × 1010 vector genomes [vg]/eye), cotoretigene toliparvovec high dose (2.5 × 1011 vg/eye), or untreated control. MAIN OUTCOME MEASURES: The primary endpoint was the percentage of participants meeting microperimetry responder criteria (≥7 dB improvement at ≥5 of 16 central loci). Secondary endpoints included change from baseline in retinal sensitivity at the central 16 loci and the entire 68 loci at 12 months and change from baseline in low-luminance visual acuity (LLVA) at 12 months; and the proportion of eyes with a ≥15 and ≥10 LLVA ETDRS letter change from baseline at month 12. RESULTS: Because of the impact of COVID-19, enrollment ended before reaching the initial target, leaving the trial underpowered. Twenty-nine participants were included (low dose n=10, high dose n=10, control n=9). At month 12, the percentage of participants meeting microperimetry responder criteria was not significantly different between cotoretigene toliparvovec (low dose, 37.5%, P=0.3181; high dose, 25.0%, P=0.5177) and control (22.2%). Mean change from baseline in microperimetry sensitivity, however, significantly improved with the low dose versus control at month 12 (P=0.0350). Significant improvement in LLVA occurred with low dose versus control at month 12 (33.3% difference [80% CI, 14.7-55.2]; P=0.0498). Three ocular-related serious adverse events occurred in the low-dose group versus 7 in the high-dose group. CONCLUSIONS: The primary microperimetry endpoint was not met. Significant improvements in LLVA and mean microperimetry and fewer serious adverse events were observed with low-dose cotoretigene toliparvovec.

Night vision restored in days after decades of congenital blindness.

Signaling of vision to the brain starts with the retinal phototransduction cascade which converts visible light from the environment into chemical changes. Vision impairment results when mutations inactivate proteins of the phototransduction cascade. A severe monogenically inherited blindness, Leber congenital amaurosis (LCA), is caused by mutations in the GUCY2D gene, leading to a molecular defect in the production of cyclic GMP, the second messenger of phototransduction. We studied two patients with GUCY2D-LCA who were undergoing gene augmentation therapy. Both patients had large deficits in rod photoreceptor-based night vision before intervention. Within days of therapy, rod vision in both patients changed dramatically; improvements in visual function and functional vision in these hyper-responding patients reached more than 3 log10 units (1000-fold), nearing healthy rod vision. Quick activation of the complex molecular pathways from retinal photoreceptor to visual cortex and behavior is thus possible in patients even after being disabled and dormant for decades.

Acute Macular Neuroretinopathy Following COVID-19 mRNA Vaccination.

A 21-year-old female developed bilateral acute-onset paracentral scotomas three days after receiving the second dose of her Moderna COVID-19 vaccination. A clinical diagnosis of acute macular neuroretinopathy (AMN) was confirmed after classic findings were demonstrated on near-infrared reflectance imaging, spectral-domain optical coherence tomography, and colored fundus photography. The patient presented with visual acuity of 20/100-1 OD and 20/20 OS. After treatment with brimonidine and difluprednate, at a two-week follow-up, her visual acuity was 20/100-2 OD and 20/25-2 OS. There have been reported cases of AMN following flu-like illnesses as well as after receiving vaccines. However, this is the first report of AMN following vaccination with a Moderna COVID-19 vaccine.

Baseline Microperimetry and OCT in the RUSH2A Study: Structure-Function Association and Correlation With Disease Severity.

PURPOSE: To investigate baseline mesopic microperimetry (MP) and spectral domain optical coherence tomography (OCT) in the Rate of Progression in USH2A-related Retinal Degeneration (RUSH2A) study. DESIGN: Natural history study METHODS: Setting: 16 clinical sites in Europe and North AmericaStudy Population: Participants with Usher syndrome type 2 (USH2) (N = 80) or autosomal recessive nonsyndromic RP (ARRP) (N = 47) associated with biallelic disease-causing sequence variants in USH2AObservation Procedures: General linear models were used to assess characteristics including disease duration, MP mean sensitivity and OCT intact ellipsoid zone (EZ) area. The associations between mean sensitivity and EZ area with other measures, including best corrected visual acuity (BCVA) and central subfield thickness (CST) within the central 1 mm, were assessed using Spearman correlation coefficients. MAIN OUTCOME MEASURES: Mean sensitivity on MP; EZ area and CST on OCT. RESULTS: All participants (N = 127) had OCT, while MP was obtained at selected sites (N = 93). Participants with Usher syndrome type 2 (USH2, N = 80) and nonsyndromic autosomal recessive Retinitis Pigmentosa (ARRP, N = 47) had the following similar measurements: EZ area (median (interquartile range [IQR]): 1.4 (0.4, 3.1) mm2 vs 2.3 (0.7, 5.7) mm2) and CST (median (IQR): 247 (223, 280) µm vs 261 (246, 288), and mean sensitivity (median (IQR): 3.5 (2.1, 8.4) dB vs 5.1 (2.9, 9.0) dB). Longer disease duration was associated with smaller EZ area (P < 0.001) and lower mean sensitivity (P = 0.01). Better BCVA, larger EZ area, and larger CST were correlated with greater mean sensitivity (r > 0.3 and P < 0.01). Better BCVA and larger CST were associated with larger EZ area (r > 0.6 and P < 0.001). CONCLUSIONS: Longer disease duration correlated with more severe retinal structure and function abnormalities, and there were associations between MP and OCT metrics. Monitoring changes in retinal structure-function relationships during disease progression will provide important insights into disease mechanism in USH2A-related retinal degeneration.

Tissue-specific genotype-phenotype correlations among USH2A-related disorders in the RUSH2A study.

We assessed genotype-phenotype correlations among the visual, auditory, and olfactory phenotypes of 127 participants with Usher syndrome (USH2) (n =80) or nonsyndromic autosomal recessive retinitis pigmentosa (ARRP) (n = 47) due to USH2A variants, using clinical data and molecular diagnostics from the Rate of Progression in USH2A Related Retinal Degeneration (RUSH2A) study. USH2A truncating alleles were associated with USH2 and had a dose-dependent effect on hearing loss severity with no effect on visual loss severity within the USH2 subgroup. A group of missense alleles in an interfibronectin domain appeared to be hypomorphic in ARRP. These alleles were associated with later age of onset, larger visual field area, better sensitivity thresholds, and better electroretinographic responses. No effect of genotype on the severity of olfactory deficits was observed. This study unveils a unique, tissue-specific USH2A allelic hierarchy with important prognostic implications for patient counseling and treatment trial endpoints. These findings may inform clinical care or research approaches in others with allelic disorders or pleiotropic phenotypes.

Unusual Presentation of Presumed Arteritic Ischemic Optic Neuropathy in Waxy Pale Disc of Retinitis Pigmentosa.

This case report describes an unusual presentation of arteritic anterior ischemic optic neuropathy (AAION) in a 68-year-old patient with retinitis pigmentosa (RP) secondary to Usher syndrome. The authors report a patient with RP who presented with rapid unilateral vision loss. A diagnosis of AAION was made by fluorescein angiography and temporal artery biopsy despite the lack of typical optic nerve features of anterior ischemic neuropathy, which were likely masked due to the waxy pale disc associated with RP. [Ophthalmic Surg Lasers Imaging Retina. 2021;52:350-352.].

Examining Whether AOSLO-Based Foveal Cone Metrics in Achromatopsia and Albinism Are Representative of Foveal Cone Structure.

Purpose: Adaptive optics scanning light ophthalmoscopy (AOSLO) imaging in patients with achromatopsia (ACHM) and albinism is not always successful. Here, we tested whether optical coherence tomography (OCT) measures of foveal structure differed between patients for whom AOSLO images were either quantifiable or unquantifiable. Methods: The study included 166 subjects (84 with ACHM; 82 with albinism) with previously acquired OCT scans, AOSLO images, and best-corrected visual acuity (BCVA, if available). Foveal OCT scans were assessed for outer retinal structure, outer nuclear layer thickness, and hypoplasia. AOSLO images were graded as quantifiable if a peak cone density could be measured and/or usable if the location of peak density could be identified and the parafoveal mosaic was quantifiable. Results: Forty-nine percent of subjects with ACHM and 57% of subjects with albinism had quantifiable AOSLO images. Older age and better BCVA were found in subjects with quantifiable AOSLO images for both ACHM (P = 0.0214 and P = 0.0276, respectively) and albinism (P = 0.0073 and P < 0.0004, respectively). There was a significant trend between ellipsoid zone appearance and ability to quantify AOSLO (P = 0.0028). In albinism, OCT metrics of cone structure did not differ between groups. Conclusions: Previously reported AOSLO-based cone density measures in ACHM may not necessarily reflect the degree of remnant cone structure in these patients. Translational Relevance: Until AOSLO is successful in all patients with ACHM and albinism, the possibility of the reported data from a particular cohort not being representative of the entire population remains an important issue to consider when interpreting results from AOSLO studies.

Optical Coherence Tomography Artifacts Are Associated With Adaptive Optics Scanning Light Ophthalmoscopy Success in Achromatopsia.

Purpose: To determine whether artifacts in optical coherence tomography (OCT) images are associated with the success or failure of adaptive optics scanning light ophthalmoscopy (AOSLO) imaging in subjects with achromatopsia (ACHM). Methods: Previously acquired OCT and non-confocal, split-detector AOSLO images from one eye of 66 subjects with genetically confirmed achromatopsia (15 CNGA3 and 51 CNGB3) were reviewed along with best-corrected visual acuity (BCVA) and axial length. OCT artifacts in interpolated vertical volumes from CIRRUS macular cubes were divided into four categories: (1) none or minimal, (2) clear and low frequency, (3) low amplitude and high frequency, and (4) high amplitude and high frequency. Each vertical volume was assessed once by two observers. AOSLO success was defined as sufficient image quality in split-detector images at the fovea to assess cone quantity. Results: There was excellent agreement between the two observers for assessing OCT artifact severity category (weighted kappa = 0.88). Overall, AOSLO success was 47%. For subjects with OCT artifact severity category 1, AOSLO success was 65%; for category 2, 47%; for category 3, 11%; and for category 4, 0%. There was a significant association between OCT artifact severity category and AOSLO success (P = 0.0002). Neither BCVA nor axial length was associated with AOSLO success (P = 0.07 and P = 0.75, respectively). Conclusions: Artifacts in OCT volumes are associated with AOSLO success in ACHM. Subjects with less severe OCT artifacts are more likely to be good candidates for AOSLO imaging, whereas AOSLO was successful in only 7% of subjects with category 3 or 4 OCT artifacts. These results may be useful in guiding patient selection for AOSLO imaging. Translational Relevance: Using OCT to prescreen patients could be a valuable tool for clinical trials that utilize AOSLO to reduce costs and decrease patient testing burden.

Current Clinical Applications of In Vivo Gene Therapy with AAVs.

Hereditary diseases are caused by mutations in genes, and more than 7,000 rare diseases affect over 30 million Americans. For more than 30 years, hundreds of researchers have maintained that genetic modifications would provide effective treatments for many inherited human diseases, offering durable and possibly curative clinical benefit with a single treatment. This review is limited to gene therapy using adeno-associated virus (AAV) because the gene delivered by this vector does not integrate into the patient genome and has a low immunogenicity. There are now five treatments approved for commercialization and currently available, i.e., Luxturna, Zolgensma, the two chimeric antigen receptor T cell (CAR-T) therapies (Yescarta and Kymriah), and Strimvelis (the gammaretrovirus approved for adenosine deaminase-severe combined immunodeficiency [ADA-SCID] in Europe). Dozens of other treatments are under clinical trials. The review article presents a broad overview of the field of therapy by in vivo gene transfer. We review gene therapy for neuromuscular disorders (spinal muscular atrophy [SMA]; Duchenne muscular dystrophy [DMD]; X-linked myotubular myopathy [XLMTM]; and diseases of the central nervous system, including Alzheimer's disease, Parkinson's disease, Canavan disease, aromatic l-amino acid decarboxylase [AADC] deficiency, and giant axonal neuropathy), ocular disorders (Leber congenital amaurosis, age-related macular degeneration [AMD], choroideremia, achromatopsia, retinitis pigmentosa, and X-linked retinoschisis), the bleeding disorder hemophilia, and lysosomal storage disorders.

Baseline Visual Field Findings in the RUSH2A Study: Associated Factors and Correlation With Other Measures of Disease Severity.

PURPOSE: To report baseline visual fields in the Rate of Progression in USH2A-related Retinal Degeneration (RUSH2A) study. DESIGN: Cross-sectional study within a natural history study. METHODS: Setting: multicenter, international. STUDY POPULATION: Usher syndrome type 2 (USH2) (n = 80) or autosomal recessive nonsyndromic retinitis pigmentosa (ARRP) (n = 47) associated with biallelic disease-causing sequence variants in USH2A. OBSERVATION PROCEDURES: Repeatability of full-field static perimetry (SP) and between-eye symmetry of kinetic perimetry (KP) were evaluated with intraclass correlation coefficients (ICCs). The association of demographic and clinical characteristics with total hill of vision (VTOT) was assessed with general linear models. Associations between VTOT and other functional and morphologic measures were assessed using Spearman correlation coefficients and t tests. MAIN OUTCOME MEASURES: VTOT (SP) and III4e isopter area (KP). RESULTS: USH2 participants had more severe visual field loss than ARRP participants (P < .001, adjusting for disease duration, age of enrollment). Mean VTOT measures among 3 repeat tests were 32.7 ± 24.1, 31.2 ± 23.4, and 31.7 ± 23.9 decibel-steradians (intraclass correlation coefficient [ICC] = 0.96). Better VA, greater photopic ERG 30-Hz flicker amplitudes, higher mean microperimetry sensitivity, higher central subfield thickness, absence of macular cysts, and higher III4e seeing area were associated with higher VTOT (all r > .48; P < .05). Mean III4e isopter areas for left (4561 ± 4426 squared degrees) and right eyes (4215 ± 4300 squared degrees) were concordant (ICC = 0.94). CONCLUSIONS: USH2 participants had more visual field loss than participants with USH2A-related ARRP, adjusting for duration of disease and age of enrollment. VTOT was repeatable and correlated with other functional and structural metrics, suggesting it may be a good summary measure of disease severity in patients with USH2A-related retinal degeneration.

Interocular Symmetry of Foveal Cone Topography in Congenital Achromatopsia.

Purpose: To determine the interocular symmetry of foveal cone topography in achromatopsia (ACHM) using non-confocal split-detection adaptive optics scanning light ophthalmoscopy (AOSLO). Methods: Split-detector AOSLO images of the foveal cone mosaic were acquired from both eyes of 26 subjects (mean age 24.3 years; range 8-44 years, 14 females) with genetically confirmed CNGA3- or CNGB3-associated ACHM. Cones were identified within a manually delineated rod-free zone. Peak cone density (PCD) was determined using an 80 × 80 µm sampling window within the rod-free zone. The mean and standard deviation (SD) of inter-cell distance (ICD) were calculated to derive the coefficient of variation (CV). Cone density difference maps were generated to compare cone topography between eyes. Results: PCD (mean ± SD) was 17,530 ± 9,614 cones/mm2 and 17,638 ± 9,753 cones/mm2 for right and left eyes, respectively (p = .677, Wilcoxon test). The mean (± SD) for ICD was 9.05 ± 2.55 µm and 9.24 ± 2.55 µm for right and left eyes, respectively (p = .410, paired t-test). The mean (± SD) for CV of ICD was 0.16 ± 0.03 µm and 0.16 ± 0.04 µm for right and left eyes, respectively (p = .562, paired t-test). Cone density maps demonstrated that cone topography of the ACHM fovea is non-uniform with local variations in cone density between eyes. Conclusions: These results demonstrate the interocular symmetry of the foveal cone mosaic (both density and packing) in ACHM. As cone topography can differ between eyes of a subject, PCD does not completely describe the foveal cone mosaic in ACHM. Nonetheless, these findings are of value in longitudinal monitoring of patients during treatment trials and further suggest that both eyes of a given subject may have similar therapeutic potential and non-study eye can be used as a control.

Intraobserver Repeatability and Interobserver Reproducibility of Ellipsoid Zone Measurements in Retinitis Pigmentosa.

PURPOSE: To examine repeatability and reproducibility of ellipsoid zone (EZ) width measurements in patients with retinitis pigmentosa (RP) using a longitudinal reflectivity profile (LRP) analysis. METHODS: We examined Bioptigen optical coherence tomography (OCT) scans from 48 subjects with RP or Usher syndrome. Nominal scan lengths were 6, 7, or 10 mm, and the lateral scale of each scan was calculated using axial length measurements. LRPs were generated from OCT line scans, and the peak corresponding to EZ was manually identified using ImageJ. The locations at which the EZ peak disappeared were used to calculate EZ width. Each scan was analyzed twice by each of two observers, who were masked to their previous measurements and those of the other observer. RESULTS: On average, horizontal width (HW) was significantly greater than vertical width (VW), and there was high interocular symmetry for both HW and VW. We observed excellent intraobserver repeatability with intraclass correlation coefficients (ICCs) ranging from 0.996 to 0.998 for HW and VW measurements. Interobserver reproducibility was also excellent for both HW (ICC = 0.989; 95% confidence interval [CI] = 0.983-0.995) and VW (ICC = 0.991; 95% CI = 0.985-0.996), with no significant bias observed between observers. CONCLUSIONS: EZ width can be measured using LRPs with excellent repeatability and reproducibility. Our observation of greater HW than VW is consistent with previous observations in RP, though the reason for this anisotropy remains unclear. TRANSLATIONAL RELEVANCE: We describe repeatability and reproducibility of a method for measuring EZ width in patients with RP or Usher syndrome. This approach could facilitate measurement of retinal band thickness and/or intensity.

CILIOCHOROIDAL EFFUSION AND ACUTE MACULAR NEURORETINOPATHY ASSOCIATED WITH CERVICAL TRACTION THERAPY.

PURPOSE: To report an unusual case of ciliochoroidal effusion and presumed acute macular neuroretinopathy associated with cervical traction therapy for the treatment of cervical spinal stenosis. METHODS: Case report. RESULTS: A 75-year-old man reported sudden onset of a wedge-shaped paracentral scotoma in the right eye. Fundus examination showed a ciliochoroidal effusion in the right eye. Optical coherence tomography revealed intraretinal fluid in both eyes without leakage on fluorescein angiography. B-scan ultrasonography and anterior segment ultrasound biomicroscopy of the right eye showed peripheral ciliochoroidal effusion. He had recently started intensive cervical traction therapy for the treatment of cervical spinal stenosis. There was spontaneous resolution of the choroidal effusion and intraretinal fluid after stopping cervical traction treatments. Optical coherence tomography imaging after resolution of the intraretinal fluid revealed thinning of the outer nuclear layer and attenuation of the ellipsoid and interdigitation zones corresponding to a persistent paracentral scotoma, consistent with acute macular neuroretinopathy. CONCLUSION: This is the first report of adverse ocular effects of cervical traction. We postulate that venous and arterial compromise during cervical traction therapy resulted in both ciliochoroidal effusion and a watershed infarct in the outer retina.

REPEATABILITY AND LONGITUDINAL ASSESSMENT OF FOVEAL CONE STRUCTURE IN CNGB3-ASSOCIATED ACHROMATOPSIA.

PURPOSE: Congenital achromatopsia is an autosomal recessive disease causing substantial reduction or complete absence of cone function. Although believed to be a relatively stationary disorder, questions remain regarding the stability of cone structure over time. In this study, the authors sought to assess the repeatability of and examine longitudinal changes in measurements of central cone structure in patients with achromatopsia. METHODS: Forty-one subjects with CNGB3-associated achromatopsia were imaged over a period of between 6 and 26 months using optical coherence tomography and adaptive optics scanning light ophthalmoscopy. Outer nuclear layer (ONL) thickness, ellipsoid zone (EZ) disruption, and peak foveal cone density were assessed. RESULTS: ONL thickness increased slightly compared with baseline (0.184 µm/month, P = 0.02). The EZ grade remained unchanged for 34/41 subjects. Peak foveal cone density did not significantly change over time (mean change 1% per 6 months, P = 0.126). CONCLUSION: Foveal cone structure showed little or no change in this group of subjects with CNGB3-associated achromatopsia. Over the time scales investigated (6-26 months), achromatopsia seems to be a structurally stable condition, although longer-term follow-up is needed. These data will be useful in assessing foveal cone structure after therapeutic intervention.

Residual Foveal Cone Structure in CNGB3-Associated Achromatopsia.

PURPOSE: Congenital achromatopsia (ACHM) is an autosomal recessive disorder in which cone function is absent or severely reduced. Gene therapy in animal models of ACHM have shown restoration of cone function, though translation of these results to humans relies, in part, on the presence of viable cone photoreceptors at the time of treatment. Here, we characterized residual cone structure in subjects with CNGB3-associated ACHM. METHODS: High-resolution imaging (optical coherence tomography [OCT] and adaptive optics scanning light ophthalmoscopy [AOSLO]) was performed in 51 subjects with CNGB3-associated ACHM. Peak cone density and inter-cone spacing at the fovea was measured using split-detection AOSLO. Foveal outer nuclear layer thickness was measured in OCT images, and the integrity of the photoreceptor layer was assessed using a previously published OCT grading scheme. RESULTS: Analyzable images of the foveal cones were obtained in 26 of 51 subjects, with nystagmus representing the major obstacle to obtaining high-quality images. Peak foveal cone density ranged from 7,273 to 53,554 cones/mm2, significantly lower than normal (range, 84,733-234,391 cones/mm2), with the remnant cones being either contiguously or sparsely arranged. Peak cone density was correlated with OCT integrity grade; however, there was overlap of the density ranges between OCT grades. CONCLUSIONS: The degree of residual foveal cone structure varies greatly among subjects with CNGB3-associated ACHM. Such measurements may be useful in estimating the therapeutic potential of a given retina, providing affected individuals and physicians with valuable information to more accurately assess the risk-benefit ratio as they consider enrolling in experimental gene therapy trials. (www.clinicaltrials.gov, NCT01846052.).

Assessing Photoreceptor Structure in Retinitis Pigmentosa and Usher Syndrome.

PURPOSE: The purpose of this study was to examine cone photoreceptor structure in retinitis pigmentosa (RP) and Usher syndrome using confocal and nonconfocal split-detector adaptive optics scanning light ophthalmoscopy (AOSLO). METHODS: Nineteen subjects (11 RP, 8 Usher syndrome) underwent ophthalmic and genetic testing, spectral-domain optical coherence tomography (SD-OCT), and AOSLO imaging. Split-detector images obtained in 11 subjects (7 RP, 4 Usher syndrome) were used to assess remnant cone structure in areas of altered cone reflectivity on confocal AOSLO. RESULTS: Despite normal interdigitation zone and ellipsoid zone appearance on OCT, foveal and parafoveal cone densities derived from confocal AOSLO images were significantly lower in Usher syndrome compared with RP. This was due in large part to an increased prevalence of non-waveguiding cones in the Usher syndrome retina. Although significantly correlated to best-corrected visual acuity and foveal sensitivity, cone density can decrease by nearly 38% before visual acuity becomes abnormal. Aberrantly waveguiding cones were noted within the transition zone of all eyes and corresponded to intact inner segment structures. These remnant cones decreased in density and increased in diameter across the transition zone and disappeared with external limiting membrane collapse. CONCLUSIONS: Foveal cone density can be decreased in RP and Usher syndrome before visible changes on OCT or a decline in visual function. Thus, AOSLO imaging may allow more sensitive monitoring of disease than current methods. However, confocal AOSLO is limited by dependence on cone waveguiding, whereas split-detector AOSLO offers unambiguous and quantifiable visualization of remnant cone inner segment structure. Confocal and split-detector thus offer complementary insights into retinal pathology.

Evaluating Efficacy of Aflibercept in Refractory Exudative Age-Related Macular Degeneration With OCT Segmentation Volumetric Analysis.

BACKGROUND AND OBJECTIVE: To use automated segmentation software to analyze spectral-domain optical coherence tomography (SD-OCT) scans and evaluate the effectiveness of aflibercept (Eylea; Regeneron, Tarrytown, NY) in the treatment of patients with exudative age-related macular degeneration (AMD) refractory to other treatments. PATIENTS AND METHODS: Retrospective chart review of 16 patients refractory to bevacizumab (Avastin; Genentech, South San Francisco, CA)/ranibizumab (Lucentis; Genentech, San Francisco, CA) treatment was conducted. Visual acuity, central foveal thickness (CFT), maximum fluid height, pigment epithelial detachment (PED) volume, sub-retinal fluid (SRF) volume, fluid-free time interval, and adverse effects were evaluated. Automated segmentation analysis was used to quantify improvement. RESULTS: With aflibercept treatment, there was a statistically significant improvement in visual acuity by 1 line (P = .020), in CFT by 74.02 µm (P = .001), and in maximum fluid height by 31.9 µm (P= .011). Total PED and SRF volume also decreased significantly by 1.50 µm(3) × 10(8) µm(3) (P = .013). Anatomic improvement was confirmed by automated segmentation analysis. CONCLUSION: This study demonstrates utility of automated segmentation software in quantifying anatomic improvement with aflibercept treatment in exudative AMD refractory to other anti-vascular endothelial growth factor treatments.

Role for rapid surgical intervention in uveal effusion syndrome with associated optic neuropathy.

Uveal effusion syndrome (UES) can be associated with nanophthalmos and rarely can present with concomitant optic neuropathy. This case report describes nanophthalmic UES and optic neuropathy treated with early sclerectomies. One month postoperatively, the patient experienced significant improvement in choroidal effusions and optic neuropathy, with increases in visual acuity and visual fields. Early scleral windows surgery for UES with associated optic neuropathy can provide prompt improvement of choroidal swelling, optic nerve edema, and vision, although the relapsing course of this disease presents a challenge to long-term visual prognosis.

Spectral domain optical coherence tomography findings in CNGB3-associated achromatopsia and therapeutic implications.

We describe the spectral domain OCT findings in two siblings with CNGB3-associated achromatopsia. A 33-year-old female and her 31-year-old sibling were evaluated for mild nystagmus and decreased visual acuity which had been present since childhood. They were each evaluated with full field Ganzfeld electroretinography which demonstrated flat photopic responses and preserved rod function. Genetic testing performed at Carver lab at the University of Iowa confirmed a diagnosis of achromatopsia with identical mutations in the CNGB3 gene. Spectral domain optical coherence tomography was performed which revealed foveal changes in both siblings, with slight phenotypic variations in these genotypically identical siblings. OCT findings in achromatopsia emphasize the importance of early identification and treatment in this disorder.