A Retrospective Longitudinal Study of 460 Patients with ABCA4-Associated Retinal Disease.

PURPOSE: To investigate the distribution of genotypes and natural history of ABCA4-associated retinal disease in a large cohort of patients seen at a single institution. DESIGN: Retrospective, single-institution cohort review. PARTICIPANTS: Patients seen at the University of Iowa between November 1986 and August 2022 clinically suspected to have disease caused by sequence variations in ABCA4. METHODS: DNA samples from participants were subjected to a tiered testing strategy progressing from allele-specific screening to whole genome sequencing. Charts were reviewed, and clinical data were tabulated. The pathogenic severity of the most common alleles was estimated by studying groups of patients who shared 1 allele. Groups of patients with shared genotypes were reviewed for evidence of modifying factor effects. MAIN OUTCOME MEASURES: Age at first uncorrectable vision loss, best-corrected visual acuity, and the area of the I2e isopter of the Goldmann visual field. RESULTS: A total of 460 patients from 390 families demonstrated convincing clinical features of ABCA4-associated retinal disease. Complete genotypes were identified in 399 patients, and partial genotypes were identified in 61. The median age at first vision loss was 16 years (range, 4-76 years). Two hundred sixty-five families (68%) harbored a unique genotype, and no more than 10 patients shared any single genotype. Review of the patients with shared genotypes revealed evidence of modifying factors that in several cases resulted in a > 15-year difference in age at first vision loss. Two hundred forty-one different alleles were identified among the members of this cohort, and 161 of these (67%) were found in only a single individual. CONCLUSIONS: ABCA4-associated retinal disease ranges from a very severe photoreceptor disease with an onset before 5 years of age to a late-onset retinal pigment epithelium-based condition resembling pattern dystrophy. Modifying factors frequently impact the ABCA4 disease phenotype to a degree that is similar in magnitude to the detectable ABCA4 alleles themselves. It is likely that most patients in any cohort will harbor a unique genotype. The latter observations taken together suggest that patients' clinical findings in most cases will be more useful for predicting their clinical course than their genotype. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

EVALUATION OF RETINAL DISPLACEMENT FOLLOWING PRIMARY SCLERAL BUCKLING FOR MACULA-INVOLVING RHEGMATOGENOUS RETINAL DETACHMENT.

PURPOSE: To evaluate the incidence and degree of retinal displacement following scleral buckling surgery for macula-involving rhegmatogenous retinal detachment. METHODS: Retrospective interventional case series comprised of patients treated with primary scleral buckling procedure without gas tamponade for macula-involving rhegmatogenous retinal detachment and imaged postoperatively with fundus autofluorescence imaging between June 1, 2016 and July 25, 2021. Clinical notes, operative reports, fundus autofluorescence photographs, and optical coherence tomography images were reviewed. The presence and degree of retinal displacement were recorded. RESULTS: Twelve eyes of 11 patients were included. One (8%) eye with an epiretinal membrane demonstrated 0.1 mm of retinal displacement along the superior arcade and in the superotemporal periphery. The remainder of eyes (92%) did not show any identifiable signs of retinal displacement. CONCLUSION: Retinal displacement does not seem to be a frequent complication of primary scleral buckling surgery for macula-involving rhegmatogenous retinal detachment.

LONGITUDINAL ANALYSIS OF DIABETIC CHOROIDOPATHY IN PROLIFERATIVE DIABETIC RETINOPATHY TREATED WITH PANRETINAL PHOTOCOAGULATION USING WIDEFIELD SWEPT-SOURCE OPTICAL COHERENCE TOMOGRAPHY.

PURPOSE: Widefield swept-source optical coherence tomography (OCT) imaging was used to characterize choroidal thickness and vascularity at baseline in proliferative diabetic retinopathy (PDR) and longitudinally after panretinal photocoagulation (PRP). METHODS: Patients with treatment-naive PDR were imaged at baseline and at 1 week, 1 month, and 3 months after PRP. Previously validated algorithms were used to calculate the mean choroidal thickness (MCT) and choroidal vascularity index (CVI) in 5 regions of 12 mm × 12 mm scans. RESULTS: Fourteen PDR eyes were included. Baseline MCT in PDR eyes did not differ significantly from normal eyes, but CVI measurements in PDR eyes were lower in all regions (P < 0.001-0.008). After PRP, MCT measurements in PDR eyes were significantly lower at 1 month and 3 months in all regions (P < 0.001-0.005) except the fovea (P = 0.074). However, CVI measurements did not change over time in any region after PRP. CONCLUSION: The choroid in PDR eyes has a smaller CVI than that in normal eyes. After PRP, the choroidal thickness decreases outside the fovea, but the CVI remains constant, which suggests that a relative decrease in choroidal vascularity persists. These widefield swept-source OCT results are consistent with choroidal alterations found in histopathological reports of diabetic choroidopathy.

Episodic neurologic disorders: syndromes, genes, and mechanisms.

Many neurologic diseases cause discrete episodic impairment in contrast with progressive deterioration. The symptoms of these episodic disorders exhibit striking variety. Herein we review what is known of the phenotypes, genetics, and pathophysiology of episodic neurologic disorders. Of these, most are genetically complex, with unknown or polygenic inheritance. In contrast, a fascinating panoply of episodic disorders exhibit Mendelian inheritance. We classify episodic Mendelian disorders according to the primary neuroanatomical location affected: skeletal muscle, cardiac muscle, neuromuscular junction, peripheral nerve, or central nervous system (CNS). Most known Mendelian mutations alter genes that encode membrane-bound ion channels. These mutations cause ion channel dysfunction, which ultimately leads to altered membrane excitability as manifested by episodic disease. Other Mendelian disease genes encode proteins essential for ion channel trafficking or stability. These observations have cemented the channelopathy paradigm, in which episodic disorders are conceptualized as disorders of ion channels. However, we expand on this paradigm to propose that dysfunction at the synaptic and neuronal circuit levels may underlie some episodic neurologic entities.

Toward a New Staging System for Diabetic Retinopathy Using Wide Field Swept-Source Optical Coherence Tomography Angiography.

PURPOSE OF REVIEW: For over 50 years, diabetic retinopathy (DR) has been classified by pathologic features seen on clinical examination and conventional retinal photographs. However, newer technology such as optical coherence tomography angiography (OCTA) now enables rapid acquisition of retinal structural and vascular information in a reliable, non-invasive, high-resolution fashion. Here, we highlight recent studies that have explored wide field swept-source OCTA (WF SS-OCTA) for the diagnosis and management of DR. RECENT FINDINGS: Multiple studies have demonstrated the utility of WF SS-OCTA for detection of all clinically relevant features of DR. An updated DR staging system is proposed that leverages the advantages of WF SS-OCTA, including the ability to correlate detailed vascular and structural pathology over time with longitudinal imaging. WF SS-OCTA has tremendous potential for evaluating patients with DR. A new WF SS-OCTA-based staging system may be useful in routine clinical practice and for clinical trials.

CLINICOPATHOLOGIC CORRELATION OF PRERETINAL TISSUES IN MYOPIC TRACTION MACULOPATHY.

PURPOSE: To evaluate histopathologic features of preretinal tissues removed from eyes with myopic traction maculopathy (MTM). METHODS: We retrospectively studied preretinal tissue specimens from eyes with MTM removed during pars plana vitrectomy. A control group of six idiopathic epiretinal membranes was studied for comparison. RESULTS: Six MTM specimens were studied histopathologically. Outer retinal schisis-like thickening was present in 100% of preoperative optical coherence tomography images; four of the six eyes had subfoveal neurosensory retinal detachment. Postoperative optical coherence tomography images demonstrated complete resolution of the schisis-like appearance in all eyes; a full-thickness macular hole occurred in two of the six eyes. Histopathologic examination disclosed fibrocellular tissue that was strongly positive for glial fibrillary acidic protein, weak to moderately positive for cytokeratin, and weakly positive for smooth muscle actin and CD68. There were no apparent histopathologic or immunohistochemical differences between preretinal tissues from eyes with MTM and idiopathic epiretinal membranes from control eyes. CONCLUSION: The outer retinal schisis-like thickening, commonly associated with subretinal fluid, that characterizes MTM is associated with preretinal tissues that are histopathologically indistinguishable from idiopathic epiretinal membranes. These findings suggest that anteroposterior traction caused by axial elongation rather than a uniquely abnormal cellular process is the etiologic mechanism of MTM.

WIDE-FIELD SWEPT-SOURCE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY OF DIABETIC TRACTIONAL RETINAL DETACHMENTS BEFORE AND AFTER SURGICAL REPAIR.

PURPOSE: Wide-field (WF) swept-source (SS) optical coherence tomography angiography (SS-OCTA) was used to image diabetic tractional retinal detachments (TRDs) before and after pars plana vitrectomy. The clinical utility of SS-OCTA was assessed. METHODS: Patients with diabetic TRDs were imaged prospectively with SS-OCTA. Ultrawide-field imaging was obtained when possible. Postoperative WF SS-OCTA imaging was performed. RESULTS: From January 2018 through December 2019, 31 eyes of 21 patients with diabetic TRDs were imaged. Wide-field SS-OCTA en-face images captured all areas of TRD and fibrovascular proliferation within the posterior pole that were visualized on ultrawide-field imaging. Optical coherence tomography angiography B-scans revealed the vascularity of preretinal membranes and identified areas of vitreoretinal traction and posterior vitreous detachment. Ten eyes underwent pars plana vitrectomy. Postoperative SS-OCTA imaging demonstrated removal of fibrovascular membranes, relief of traction, and resolution of TRDs. Retinal ischemia before and after surgical repair appeared similar. CONCLUSION: All clinically relevant features of diabetic TRDs were identified at baseline and assessed longitudinally after pars plana vitrectomy using WF SS-OCTA, which showed resolution of vitreoretinal traction and no apparent change in the status of retinal perfusion after surgery. If the media are clear and fixation is adequate, WF SS-OCTA is likely the only imaging modality needed for the diagnosis and longitudinal evaluation of diabetic TRDs.

Masqueraders of multiple evanescent white dot syndrome (MEWDS).

PURPOSE: To describe disorders that can masquerade as multiple evanescent white dot syndrome (MEWDS). DESIGN: Retrospective, multicenter case series. PARTICIPANTS: Patients who presented with clinical findings compatible with a diagnosis of MEWDS but were ultimately diagnosed with an alternative inflammatory, infectious, or neoplastic disorder. METHODS: Clinical records and multimodal imaging findings including fundus photography, fundus autofluorescence (FAF), fluorescein angiography (FA), indocyanine green angiography (ICGA), optical coherence tomography (OCT), and OCT angiography (OCTA) were analyzed. MAIN OUTCOME MEASURES: Inclusion criteria to be defined as a masquerade syndrome for MEWDS included the presence of disseminated grayish-white outer retinal spots that were hyperautofluorescent on FAF and associated with ellipsoid zone (EZ) disruption on OCT. RESULTS: Twenty-two eyes of 13 patients were identified. All patients presented with the classic findings of MEWDS listed above. A MEWDS-like presentation was bilateral in nine of 13 patients (69%). Final diagnosis was determined on the basis of additional investigations including serologies and biopsy. These diagnoses included syphilis (three patients), lymphoma (three patients), idiopathic multifocal choroiditis (two patients), idiopathic retinal phlebitis (one patient), idiopathic acute zonal occult outer retinopathy (one patient), sarcoidosis (one patient), tuberculosis (one patient), and cancer-associated retinopathy (one patient). The outer retinal lesions and imaging findings resolved with treatment for the associated systemic disorders. CONCLUSIONS: Widespread grayish-white outer retinal spots associated with hyperautofluorescence on FAF and disruption of the EZ on OCT are not pathognomonic for MEWDS. A high index of suspicion must be maintained for masqueraders of MEWDS, which can include serious inflammatory, infectious, and neoplastic disorders.

High Dynamic Range Image Processing for Retinal Color Fundus Photography.

BACKGROUND AND OBJECTIVE: Color fundus photography is an important imaging modality that is currently limited by a narrow dynamic range. We describe a post-image processing technique to generate high dynamic range (HDR) retinal images with enhanced detail. PATIENTS AND METHODS: This was a retrospective, observational case series evaluating fundus photographs of patients with macular pathology. Photographs were acquired with three or more exposure values using a commercially available camera (Topcon 50-DX). Images were aligned and imported into HDR processing software (Photomatix Pro). Fundus detail was compared between HDR and raw photographs. RESULTS: Sixteen eyes from 10 patients (5 male, 5 female; mean age 59.4 years) were analyzed. Clinician graders preferred the HDR image 91.7% of the time (44/48 image comparisons), with good grader agreement (81.3%, 13/16 eyes). CONCLUSIONS: HDR fundus imaging is feasible using images from existing fundus cameras and may be useful for enhanced visualization of retinal detail in a variety of pathologic states. [Ophthalmic Surg Lasers Imaging Retina 2024;55:263-269.].

Familial cortical myoclonus with a mutation in NOL3.

OBJECTIVE: Myoclonus is characterized by sudden, brief involuntary movements, and its presence is debilitating. We identified a family suffering from adult onset, cortical myoclonus without associated seizures. We performed clinical, electrophysiological, and genetic studies to define this phenotype. METHODS: A large, 4-generation family with a history of myoclonus underwent careful questioning, examination, and electrophysiological testing. Thirty-five family members donated blood samples for genetic analysis, which included single nucleotide polymorphism mapping, microsatellite linkage, targeted massively parallel sequencing, and Sanger sequencing. In silico and in vitro experiments were performed to investigate functional significance of the mutation. RESULTS: We identified 11 members of a Canadian Mennonite family suffering from adult onset, slowly progressive, disabling, multifocal myoclonus. Somatosensory evoked potentials indicated a cortical origin of the myoclonus. There were no associated seizures. Some severely affected individuals developed signs of progressive cerebellar ataxia of variable severity late in the course of their illness. The phenotype was inherited in an autosomal dominant fashion. We demonstrated linkage to chromosome 16q21-22.1. We then sequenced all coding sequence in the critical region, identifying only a single cosegregating, novel, nonsynonymous mutation, which resides in the gene NOL3. Furthermore, this mutation was found to alter post-translational modification of NOL3 protein in vitro. INTERPRETATION: We propose that familial cortical myoclonus is a novel movement disorder that may be caused by mutation in NOL3. Further investigation of the role of NOL3 in neuronal physiology may shed light on neuronal membrane hyperexcitability and pathophysiology of myoclonus and related disorders.

Improved Visual Outcomes after Severe Open-Globe Injuries Associated with Perioperative Vitreoretinal Evaluation.

PURPOSE: To investigate the impact of perioperative evaluation by a vitreoretinal surgeon on outcomes after severe open-globe injury (OGI). DESIGN: Retrospective, comparative study. SUBJECTS: Open-globe injury cohorts from 2 academic United States ophthalmology departments with disparate OGI management protocols and vitreoretinal referral patterns. METHODS: Patients with severe OGI (presenting visual acuity [VA] of counting fingers or worse) from the University of Iowa Hospitals and Clinics (UIHC) were compared with patients with severe OGI from the Bascom Palmer Eye Institute (BPEI). At UIHC, almost all cases of OGI were repaired by anterior segment surgeons, with postoperative vitreoretinal referral at the surgeon's discretion. In contrast, at BPEI, all OGIs were both repaired and managed postoperatively by a vitreoretinal surgeon. MAIN OUTCOME MEASURES: Rate of vitreoretinal surgeon evaluation, rate of pars plana vitrectomy (PPV) (either primary or secondary), and VA at the last follow-up. RESULTS: Overall, 74 subjects from UIHC and 72 subjects from BPEI met the inclusion criteria. There were no differences in preoperative VA or rates of vitreoretinal pathology. The rate of vitreoretinal surgeon evaluation was 100% at BPEI and 65% at UIHC (P < 0.001), and the rate of PPV was 71% at BPEI and 40% at UIHC (P < 0.001). Median VA at the last follow-up in the BPEI cohort was 1.35 logarithm of the minimum angle of resolution (logMAR) (interquartile range [IQR], 0.53-2.30, corresponding to a Snellen VA of ∼ 20/500) compared with a median VA of 2.70 logMAR (IQR, 0.93-2.92, corresponding to a Snellen VA of light perception) in the UIHC cohort (P = 0.031). Overall, 68% of patients in the BPEI cohort had an improvement in VA from presentation to last follow-up versus 43% in the UIHC cohort (P = 0.004). CONCLUSIONS: Automatic perioperative evaluation by a vitreoretinal surgeon was associated with a higher rate of PPV and improved visual outcomes. Prompt evaluation by a vitreoretinal surgeon, either preoperatively or in the early postoperative period, should be considered, when logistically feasible, in severe OGIs because PPV is frequently indicated and may result in significant visual improvement. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Xp11.3 microdeletion causing Norrie disease and X-linked Kabuki syndrome.

Purpose: To describe a novel case of Norrie disease and X-linked Kabuki syndrome caused by a microdeletion encompassing multiple genes on the X chromosome. Observations: A 3-day-old boy born at full term had bilateral retrolental fibrovascular plaques. Surgery with lensectomy and vitrectomy revealed bilateral, closed funnel retinal detachments consistent with a clinical diagnosis of Norrie disease. In addition, the baby had congenital heart defects, hearing loss, and dysmorphic facies. His mother carried a clinical diagnosis of Kabuki syndrome. Genetic testing of the baby revealed an Xp11.3 microdeletion that included the NDP and KDM6A genes, confirming the baby had both Norrie disease and X-linked Kabuki syndrome. The mother was found via ultrawide-field fluorescein angiography to have asymptomatic peripheral retinal vascular anomalies, consistent with NDP-associated familial exudative vitreoretinopathy (FEVR). Conclusions and importance: This is the first reported case of Norrie disease together with X-linked Kabuki syndrome. Contiguous gene deletions may explain some of the variable systemic involvement in Norrie disease.

Randomized Controlled Study of Cooled vs Room-Temperature Artificial Tears for Reducing Ocular Surface Irritation After Intravitreal Injection.

Purpose: To evaluate the efficacy of cooled vs room-temperature artificial tears in reducing ocular discomfort after intravitreal injections (IVIs). Methods: Patients receiving a standard intravitreal injection in the retina clinic who met the eligibility criteria and provided informed consented were enrolled in the study. Patients were randomized to the cooled tears or room-temperature tears intervention group. Both groups rated their ocular discomfort following IVI after cooled or room-temperature tears were administered. Results: The cooled group comprised 48 patients and the room-temperature group, 61 patients. There was no significant difference in the reduction of ocular discomfort between the cooled vs room-temperature artificial tears groups (P = .387). In addition, there was a similar level of reduction in ocular discomfort after either intervention (P = .681) regardless of whether or not the patients routinely used artificial tears after previous IVIs. Conclusions: Cooled tears provided no additional benefit in reducing ocular discomfort post-IVI compared with room-temperature tears. Baseline tear use after an IVI may have no true benefit other than a potential placebo effect, recall bias, or both.

Choroidal Neovascularization Is Common in Best Vitelliform Macular Dystrophy and Plays a Role in Vitelliform Lesion Evolution.

OBJECTIVE: Choroidal neovascularization (CNV) is usually considered to be a late-stage complication in Best vitelliform macular dystrophy (BVMD) and can be difficult to diagnose with fluorescein angiography. This study used swept-source (SS) OCT angiography (OCTA) to evaluate the prevalence of CNV in BVMD, identify structural features associated with CNV, and provide insight into the role of CNV in vitelliform lesion evolution. DESIGN: Institutional review board-approved, retrospective, cross-sectional, and longitudinal study. PARTICIPANTS: Patients with molecularly confirmed BVMD. METHODS: Charts from consecutive patients with BVMD imaged with SS-OCTA (PLEX Elite 9000, Carl-Zeiss Meditec Inc) at the University of Iowa from September 2017 to October 2021 were reviewed. Clinical data, including age, gender, best-corrected visual acuity (BCVA), and treatment with intravitreal anti-VEGF injections were recorded. The presence of CNV on SS-OCTA was determined by expert graders and correlated with structural features, such as interstitial fluid, subretinal fluid, nodular subretinal pillar, focal choroidal excavation (FCE), and subfoveal choroidal thickness, with a P value of < 0.05 considered statistically significant. MAIN OUTCOME MEASURES: Presence of CNV on SS-OCTA and correlation with structural features on SS-OCT. RESULTS: A total of 53 eyes from 27 patients (13 women; 48.1%) were included. The mean age was 45 years (range, 8-79 years), and the mean logarithm of the minimum angle of resolution BCVA was 0.38 (range, 0-1). Choroidal neovascularization was identified on SS-OCTA in 27 eyes (50.9%), of which 63.0% had a vitelliform (Gass stage 2) lesion. In 40.7% (11 of 27) of eyes, there was no prior clinical diagnosis of CNV. Other structural features associated with CNV included FCEs (15.1%, 8 of 53 eyes) and nodular pillars (15.1%, 8 of 53 eyes) (P < 0.01). Seven patients had available longitudinal imaging, and most of these patients had CNV visible on SS-OCTA (71.4%; 10 of 14 eyes). CONCLUSION: Choroidal neovascularization is common in BVMD, including in the early stages of the disease. The presence of FCEs or nodular pillars should heighten the clinical suspicion of CNV, which may accelerate vitelliform lesion evolution. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

The Ocular Trauma Score Underestimates Visual Recovery for the Most Severe Open-Globe Injuries.

PURPOSE: To compare visual outcomes after open-globe injury (OGI) with those predicted by the Ocular Trauma Score (OTS), and to investigate the effect of treatment with pars plana vitrectomy (PPV). DESIGN: Retrospective cohort study. SUBJECTS: Patients presenting with OGI to an academic United States ophthalmology department from 2017 to 2020. METHODS: Best-corrected visual acuity (VA) measurements at the most recent follow-up were compared with final VA predicted by the OTS, based on preoperative injury characteristics. The most recently measured VA of patients treated with PPV during initial OGI repair (primary PPV group) was compared with patients treated with PPV after initial OGI repair (secondary PPV group) and patients never treated with PPV (No PPV group). MAIN OUTCOME MEASURES: Best-corrected VA in the injured eye at last follow-up; secondary outcome measures included the occurrence of vitreous hemorrhage at any time, occurrence of retinal detachment at any time, rates of additional surgery, and rates of enucleation. RESULTS: One-hundred and thirty-three subjects with OGI were identified and analyzed. The overall rate of PPV was 32%. Predictors of worse VA at last follow-up included older age (P = 0.047) and worse presenting VA (P < 0.001). Visual acuity outcomes for eyes in OTS categories 2 to 5 did not significantly differ from OTS predictions. However, eyes in OTS category 1 had a higher likelihood of last follow-up VA of light perception (LP) to hand motion (46% in the study cohort vs. 15% predicted by the OTS, P = 0.004) and a lower likelihood of no LP (33% vs. 74%, P < 0.001). The secondary PPV group had the worst VA at presentation among the 3 groups (P = 0.016), but VA at last follow-up did not significantly differ between the study groups (P = 0.338). CONCLUSIONS: The most severe OGIs (i.e., OTS category 1) had better visual outcomes than predicted by the published OTS expectations, and secondary PPV was associated with significant visual improvement despite poor prognostic predictions. Evaluation by a vitreoretinal surgeon should be considered for all patients with severe OGI, especially those in OTS category 1. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Long-term functional and structural outcomes in X-linked retinoschisis: implications for clinical trials.

Introduction: X-linked retinoschisis (XLRS) is an inherited retinal disease (IRD) caused by pathogenic mutations in the retinoschisin gene, RS1. Affected individuals develop retinal layer separation, leading to loss of visual acuity (VA). Several XLRS gene therapy trials have been attempted but none have met their primary endpoints. An improved understanding of XLRS natural history and clinical outcomes may better inform future trials. Here, we report the long-term functional and structural outcomes of XLRS and the relevance of RS1 genotypes to the visual prognosis of affected individuals. Methods: A retrospective chart review of patients with molecularly confirmed X-linked retinoschisis was performed. Functional and structural outcomes, and RS1 genotype data, were included for analysis. Results: Fifty-two patients with XLRS from 33 families were included in the study. Median age at symptom onset was 5 years (range 0-49) and median follow-up was 5.7 years (range 0.1-56.8). Macular retinoschisis occurred in 103 of 104 eyes (99.0%), while peripheral retinoschisis occurred in 48 of 104 eyes (46.2%), most often in the inferotemporal quadrant (40.4%). Initial and final VA were similar (logMAR 0.498 vs. 0.521; p = 0.203). Fifty of 54 eyes (92.6%) developed detectable outer retinal loss by age 20, and 29 of 66 eyes (43.9%) had focal or diffuse outer retinal atrophy (ORA) by age 40. ORA but not central subfield thickness (CST) was associated with reduced VA. Inter-eye correlation was modest for VA (r-squared = 0.03; p = 0.08) and CST (r-squared = 0.15; p = 0.001). Carbonic anhydrase inhibitors (CAIs) improved CST (p = 0.026), but not VA (p = 0.380). Eight of 104 eyes (7.7%) had XLRS-related retinal detachment (RD), which was associated with poorer outcomes compared to eyes without RD (median final VA 0.875 vs. 0.487; p <0.0001). RS1 null genotypes had greater odds of at least moderate visual impairment at final follow-up (OR 7.81; 95% CI 2.17, 28.10; p = 0.002) which was independent of age at onset, initial CST, initial ORA, or previous RD. Discussion: Overall, long-term follow-up of XLRS patients demonstrated relatively stable VA, with presenting CST, development of ORA, and null RS1 mutations associated with poorer long-term visual outcomes, indicating a clinically relevant genotype-phenotype correlation in XLRS.

Modeling rod and cone photoreceptor cell survival in vivo using optical coherence tomography.

Many retinal diseases involve the loss of light-sensing photoreceptor cells (rods and cones) over time. The severity and distribution of photoreceptor loss varies widely across diseases and affected individuals, so characterizing the degree and pattern of photoreceptor loss can clarify pathophysiology and prognosis. Currently, in vivo visualization of individual photoreceptors requires technology such as adaptive optics, which has numerous limitations and is not widely used. By contrast, optical coherence tomography (OCT) is nearly ubiquitous in daily clinical practice given its ease of image acquisition and detailed visualization of retinal structure. However, OCT cannot resolve individual photoreceptors, and no OCT-based method exists to distinguish between the loss of rods versus cones. Here, we present a computational model that quantitatively estimates rod versus cone photoreceptor loss from OCT. Using histologic data of human photoreceptor topography, we constructed an OCT-based reference model to simulate outer nuclear layer thinning caused by differential loss of rods and cones. The model was able to estimate rod and cone loss using in vivo OCT data from patients with Stargardt disease and healthy controls. Our model provides a powerful new tool to quantify photoreceptor loss using OCT data alone, with potentially broad applications for research and clinical care.

Unexplained Vision Loss Associated With Intraocular Silicone Oil Tamponade in Rhegmatogenous Retinal Detachment Repair.

Purpose: To evaluate the visual outcomes with unexplained vision loss during or after silicone oil (SO) tamponade. Methods: This multicenter retrospective case series comprised patients with unexplained vision loss associated with SO tamponade or its removal. Eyes with other clear secondary identifiable causes of vision loss were excluded. Results: Twenty-nine eyes of 28 patients (64% male) were identified. The mean age was 50 ± 13 years (range, 13-78 years). The mean duration of SO tamponade was 148 ± 38 days. Eighteen eyes (62%) developed unexplained vision loss while under SO; 11 (38%) had vision loss after SO removal. The most common optical coherence tomography (OCT) finding was ganglion cell layer (GCL) thinning (55%). Eyes with vision loss after SO removal had a mean logMAR best-corrected visual acuity (BCVA) of 0.6 ± 0.7 (Snellen 20/85) before SO tamponade and 1.2 ± 0.4 (20/340) before SO removal. By the last follow-up after SO removal, the BCVA had improved to 1.1 ± 0.4 (20/235). In eyes with vision loss after SO removal, the BCVA before SO removal was 0.7 ± 0.7 (20/104), which deteriorated to 1.4 ± 0.4 (20/458) 1 month after SO removal. By the last follow-up, the BCVA had improved to 1.0 ± 0.5 (20/219). Conclusions: Unexplained vision loss can occur during SO tamponade or after SO removal. Vision loss was associated with 1000-centistoke and 5000-centistoke oil and occurred in macula-off and macula-on retinal detachments. The duration of tamponade was 3 months or longer in the majority of eyes. Most eyes had GCL thinning on OCT. Gradual visual recovery can occur yet is often incomplete.