FIVE-YEAR FUNCTIONAL OUTCOMES AFTER EPIRETINAL MEMBRANE SURGERY: A Prospective, Controlled Study.

PURPOSE: To evaluate 5-year functional outcomes involving the inner retina after epiretinal membrane (ERM) surgery. METHODS: The study eye (SE) and fellow eye (FE) of 20 patients undergoing ERM surgery were examined preoperatively and at 3, 12, 24, 36, 48, and 60 months postoperatively. Retinal nerve fiber layer and ganglion cell-inner plexiform layer (GC-IPL) thicknesses were analyzed using spectral domain optical coherence tomography. Humphrey visual field mean deviation, pattern SD, and qualitative changes were assessed and compared over time. RESULTS: Mean GC-IPL thickness in SEs was less than that of FEs at all time points with progressive thinning in SEs after ERM surgery. There was significant thinning of the superotemporal GC-IPL in SEs as compared to FEs at 3 months and 60 months (P < 0.05). Humphrey visual field mean deviation was greater in SEs as compared to FEs but statistically significant only at 0, 12, and 24 months (P < 0.05). Pattern SD increased from baseline in SEs but remained near baseline in FEs. CONCLUSION: Surgical eyes after ERM surgery demonstrated progressive thinning of the GC-IPL and transient worsening trends in Humphrey visual field mean deviation and pattern SD as compared to controls after ERM surgery.

A unique presentation of subretinal fluid in a type III torpedo maculopathy phenotype.

Purpose: To report a rare type III torpedo maculopathy lesion with a unique manifestation of subretinal fluid. Observations: A nine-year-old patient was referred to retina for an evaluation of a hypopigmented oval-shaped lesion in the temporal macula with an area of inferior subretinal fluid in the right eye. The lesion demonstrated inner and outer retinal and retinal pigment epithelial attenuation, intraretinal and subretinal fluid, a serous neurosensory retinal detachment, and inner choroidal excavation on optical coherence tomography. Fundus autofluorescence showed a lane of downward-tracking fluid. Intravenously administered fluorescein angiography revealed a window defect in the area of the torpedo lesion suggesting choroidal flush. Conclusions and Importance: The case is the third documented case of torpedo maculopathy with subretinal fluid in the literature with a unique combination of intraretinal cystic changes and dependent descending subretinal fluid, somewhat akin to a Best disease outside of the fovea with choroidal excavation. The morphology of torpedo maculopathy continues to expand as more cases are revealed.

Peripheral retinal finding on fluorescein angiography in neuronal ceroid lipofuscinosis type 2 (CLN2).

Classically, peripheral vascular changes in the retina in patients with neuronal ceroid lipofuscinosis type 2 (CLN2) are described as vascular attenuation seen in the late stages of disease on the Weill Connell Ophthalmic Severity Score (WCOSS) staging system. We describe isolated, mild, peripheral vasculitis with peripheral arteriolar dropout identified by fluorescein angiography in patients with a WCOSS grade of stage 2. We believe this vasculitis represents an early vasodegenerative phase of disease that leads to the vascular attenuation seen in later stages of the disease.

Frequency of Urgent or Emergent Vitreoretinal Surgical Procedures in the United States During the COVID-19 Pandemic.

Importance: The American Academy of Ophthalmology (AAO) indicated that urgent or emergent vitreoretinal surgical procedures should continue during the coronavirus disease 2019 (COVID-19) pandemic. Although decreases in the frequency of critical procedures have been reported outside the field of ophthalmology, analyses are limited by volume, geography, and time. Objective: To evaluate whether the frequency of ophthalmic surgical procedures deemed urgent or emergent by the AAO changed across the United States during the COVID-19 pandemic. Design, Setting, and Participants: Vitreoretinal practices from 17 institutions throughout the US participated in this multicenter cross-sectional study. The frequency of 11 billed vitreoretinal Current Procedural Terminology (CPT) codes across respective weeks was obtained from each practice between January 1, 2019, and May 31, 2020. Data were clustered into intravitreal injections (code 67028), lasers and cryotherapy (codes 67141, 67145, and 67228), retinal detachment (RD) repairs (codes 67107, 67108, 67110, and 67113), and other vitrectomies (codes 67036, 67039, and 67040). Institutions were categorized by region (Northeast, Midwest, South, and West Coast), practice setting (academic [tax-exempt] or private [non-tax-exempt]), and date of respective statewide stay-at-home orders. Main Outcomes and Measures: Nationwide changes in the frequency of billing for urgent or emergent vitreoretinal surgical procedures during the COVID-19 pandemic. Results: A total of 526 536 CPT codes were ascertained: 483 313 injections, 19 257 lasers or cryotherapy, 14 949 RD repairs, and 9017 other vitrectomies. Relative to 2019, a weekly institutional decrease in injections was observed from March 30 to May 2, 2020, with a maximal 38.6% decrease (from a mean [SD] of 437.8 [436.3] to 273.8 [269.0] injections) from April 6 to 12, 2020 (95% CI, -259 to -69 injections; P = .002). A weekly decrease was also identified that spanned a longer interval, at least until study conclusion (March 16 to May 31, 2020), for lasers and cryotherapy, with a maximal 79.6% decrease (from a mean [SD] of 6.6 [7.7] to 1.5 [2.0] procedures) from April 6 to 12, 2020 (95% CI, -6.8 to -3.3 procedures; P < .001), for RD repairs, with a maximal 59.4% decrease (from a mean [SD] of 3.5 [4.0] to 1.6 [2.2] repairs) from April 13 to 19, 2020 (95% CI, -2.7 to -1.4 repairs; P < .001), and for other vitrectomies, with a maximal 84.3% decrease (from a mean [SD] of 3.0 [3.1] to 0.4 [0.8] other vitrectomies) from April 6 to 12, 2020 (95% CI, -3.3 to -1.8 other vitrectomies; P < .001). No differences were identified by region, setting, or state-level stay-at-home order adjustment. Conclusions and Relevance: Although the AAO endorsed the continued performance of urgent or emergent vitreoretinal surgical procedures, the frequency of such procedures throughout the country experienced a substantial decrease that may persist after the COVID-19 pandemic's initial exponential growth phase. This decrease appears independent of region, setting, and state-level stay-at-home orders. It is unknown to what extent vitreoretinal intervention would have decreased without AAO recommendations, and how the decrease is associated with outcomes. Although safety is paramount during the COVID-19 pandemic, practices should consider prioritizing availability for managing high-acuity conditions until underlying reasons for the reduction are fully appreciated.

Adipose-derived stem cells from diabetic mice show impaired vascular stabilization in a murine model of diabetic retinopathy.

Diabetic retinopathy is characterized by progressive vascular dropout with subsequent vision loss. We have recently shown that an intravitreal injection of adipose-derived stem cells (ASCs) can stabilize the retinal microvasculature, enabling repair and regeneration of damaged capillary beds in vivo. Because an understanding of ASC status from healthy versus diseased donors will be important as autologous cellular therapies are developed for unmet clinical needs, we took advantage of the hyperglycemic Akimba mouse as a preclinical in vivo model of diabetic retinopathy in an effort aimed at evaluating therapeutic efficacy of adipose-derived stem cells (mASCs) derived either from healthy, nondiabetic or from diabetic mice. To these ends, Akimba mice received intravitreal injections of media conditioned by mASCs or mASCs themselves, subsequent to development of substantial retinal capillary dropout. mASCs from healthy mice were more effective than diabetic mASCs in protecting the diabetic retina from further vascular dropout. Engrafted ASCs were found to preferentially associate with the retinal vasculature. Conditioned medium was unable to recapitulate the vasoprotection seen with injected ASCs. In vitro diabetic ASCs showed decreased proliferation and increased apoptosis compared with healthy mASCs. Diabetic ASCs also secreted less vasoprotective factors than healthy mASCs, as determined by high-throughput enzyme-linked immunosorbent assay. Our findings suggest that diabetic ASCs are functionally impaired compared with healthy ASCs and support the utility of an allogeneic injection of ASCs versus autologous or conditioned media approaches in the treatment of diabetic retinopathy.

Pericytes derived from adipose-derived stem cells protect against retinal vasculopathy.

BACKGROUND: Retinal vasculopathies, including diabetic retinopathy (DR), threaten the vision of over 100 million people. Retinal pericytes are critical for microvascular control, supporting retinal endothelial cells via direct contact and paracrine mechanisms. With pericyte death or loss, endothelial dysfunction ensues, resulting in hypoxic insult, pathologic angiogenesis, and ultimately blindness. Adipose-derived stem cells (ASCs) differentiate into pericytes, suggesting they may be useful as a protective and regenerative cellular therapy for retinal vascular disease. In this study, we examine the ability of ASCs to differentiate into pericytes that can stabilize retinal vessels in multiple pre-clinical models of retinal vasculopathy. METHODOLOGY/PRINCIPAL FINDINGS: We found that ASCs express pericyte-specific markers in vitro. When injected intravitreally into the murine eye subjected to oxygen-induced retinopathy (OIR), ASCs were capable of migrating to and integrating with the retinal vasculature. Integrated ASCs maintained marker expression and pericyte-like morphology in vivo for at least 2 months. ASCs injected after OIR vessel destabilization and ablation enhanced vessel regrowth (16% reduction in avascular area). ASCs injected intravitreally before OIR vessel destabilization prevented retinal capillary dropout (53% reduction). Treatment of ASCs with transforming growth factor beta (TGF-ß1) enhanced hASC pericyte function, in a manner similar to native retinal pericytes, with increased marker expression of smooth muscle actin, cellular contractility, endothelial stabilization, and microvascular protection in OIR. Finally, injected ASCs prevented capillary loss in the diabetic retinopathic Akimba mouse (79% reduction 2 months after injection). CONCLUSIONS/SIGNIFICANCE: ASC-derived pericytes can integrate with retinal vasculature, adopting both pericyte morphology and marker expression, and provide functional vascular protection in multiple murine models of retinal vasculopathy. The pericyte phenotype demonstrated by ASCs is enhanced with TGF-ß1 treatment, as seen with native retinal pericytes. ASCs may represent an innovative cellular therapy for protection against and repair of DR and other retinal vascular diseases.

Construction of an inexpensive, hand-held fundus camera through modification of a consumer "point-and-shoot" camera.

PURPOSE: To construct a low-cost, easy-to-use, high-image-quality mydriatic fundus camera with "point-and-shoot" operation, and to evaluate the efficacy of this camera to accurately document retinal disease. METHODS: A prototype portable fundus camera was designed by interfacing a novel optical module with a Panasonic Lumix G2 consumer camera. Low-cost, commercially available optics were used to create even illumination of the fundus, providing a 50° retinal field of view. A comparative study assessing the image quality of the prototype camera against a traditional tabletop fundus camera was conducted under an Institutional Review Board (IRB)-approved study. RESULTS: A stand-alone, mydriatic camera prototype was successfully developed at a parts cost of less than $1000. The prototype camera was capable of operating in a point-and-shoot manner with automated image focusing and exposure, and the image quality of fundus photos was comparable to that of existing commercial cameras. Pathology related to both nonproliferative and proliferative diabetic retinopathy and age-related macular degeneration was easily identified from fundus images obtained from the low-cost camera. CONCLUSIONS: Early prototype development and clinical testing have shown that a consumer digital camera can be inexpensively modified to image the fundus with professional diagnostic quality. The combination of low cost, portability, point-and-shoot operation, and high image quality provides a foundational platform on which one can design an accessible fundus camera to screen for eye disease.

Attenuation of ephrinB2 reverse signaling decreases vascularized area and preretinal vascular tuft formation in the murine model of oxygen-induced retinopathy.

PURPOSE: EphB4 and ephrinB2 are known key regulators of retinal vascular development, but due to their capacity for bidirectional signaling, delineation of their individual roles in this process remains unclear. To better dissect out individual contributions, a model of proliferative retinopathy in mice with attenuated ephrinB2 reverse signaling was studied. It was hypothesized that endothelial ephrinB2 reverse signaling regulates hypoxia-induced capillary sprouting, as well as the pathologic formation of neovascular tufts in postnatal retinal microvascular networks. METHODS: Genetically manipulated mice with attenuated ephrinB2 reverse signaling (ephrinB2(lacZ/+)), along with wild-type (WT) controls, were exposed to oxygen-induced retinopathy (OIR), a postnatal model of proliferative retinopathy. At peak disease (postnatal day 18), microvascular networks were analyzed to examine intraretinal revascularization, capillary sprouting, and pathologic neovascularization responses. EphB4 and phosphorylated ephrinB protein expression patterns along retinal microvessels were also assessed. RESULTS: EphrinB2(lacZ/+) mice exhibited reduced hypoxia-induced revascularization (P ≤ 0.04) and reduced formation of neovascular tufts (P < 0.001), as compared with WT controls. Corresponding to the observed inhibition of retinal angiogenesis, ephrinB2(lacZ/+) retinas displayed an increased number of blind-ended capillary sprout tips (P < 0.02) and endothelial filopodial processes (P = 0.001). In WT and ephrinB2(lacZ/+) OIR-exposed retinas, ephrinB was confined to endothelial cells, with expression detected along angiogenic vascular processes including neovascular tufts and blind-ended capillary sprouts. CONCLUSIONS: EphrinB2 reverse signaling is a regulator of key processes during retinal vascularization and controls pathologic retinal angiogenesis through direct effects on capillary sprouting and endothelial filopodia formation.