Self-Inflicted Laser-Induced Retinopathy.

This photo essay details a patient with self-inflicted laser-induced retinal injury progressing to full-thickness macular holes in both eyes. A 40-year-old patient presented after a self-inflicted injury by a handheld class 3 blue laser (450 nm) he purchased on the internet. The patient reported shining the laser through a window, which reflected the beam back into his eyes. Visual acuity was measured at 20/400 in both eyes. The initial fundus photographs revealed vitreous and preretinal hemorrhages in the right eye, and multiple yellow-white fresh laser burns in the macula of the left eye. Optical coherence tomography (OCT) showed preretinal hemorrhage in the right eye and retinal disruption with preretinal hyper-reflective lesion in the left eye. After one month, his vision deteriorated to finger counting in each eye. He developed a full-thickness macular hole and hyperfluorescent curvilinear streaks in the superior maculae in both eyes. OCT images showed retinal pigment epithelium clumping and outer retinal atrophy in curvilinear streak areas in both eyes, which point to self-inflicted injury. This case illustrates laser-pointer-induced retinopathy and reinforces the necessity of public education on the dangers of utilizing handheld lasers without eye protection.

Surgical Management of Full-Thickness Macular Holes in Macular Telangiectasia Type 2: A Global Multicenter Study.

PURPOSE: To report on macular hole repair in macular telangiectasia type 2 (MacTel2). DESIGN: Global, multicenter, retrospective case series. PARTICIPANTS: Patients undergoing surgery for MacTel2-associated full-thickness macular hole (MTMH). METHODS: Standardized data collection sheet distributed to all surgeons. MAIN OUTCOME MEASURES: Anatomic closure and visual outcomes of MTMH. RESULTS: Sixty-three surgeries in 47 patients with MTMH were included from 30 surgeons. Mean age was 68.1 years, with 62% female, 72% White, 21% East or South Asian, 2% African American, and 2% Hispanic or Latino. Procedures included 34 internal limiting membrane (ILM) peeling alone, 22 ILM flaps, 5 autologous retinal transplantations (ARTs), 1 retinotomy, and 1 subretinal bleb. For ILM peeling, preoperative visual acuity (VA) was 0.667 ± 0.423 logarithm of the minimum angle of resolution (logMAR). Minimum hole diameter (MHD) was 305.5 ± 159.4 µm (range, 34-573 µm). Sixteen of 34 ILM peels (47%) resulted in MTMH closure. At postoperative month 6, VA was stable at 0.602 ± 0.516 logMAR (P = 0.65). VA improved by at least 2 lines in 43% and at least 4 lines in 24%. For ILM flaps, preoperative VA was 0.878 ± 0.552 logMAR. MHD was 440.8 ± 175.5 µm (range, 97-697 µm), which was significantly larger than for ILM peels (P < 0.01). Twenty of 22 ILM flaps (90%) resulted in MTMH closure, which was significantly higher than for ILM peels (P < 0.01). At postoperative month 6, VA improved to 0.555 ± 0.405 logMAR (P < 0.05). VA improved by at least 2 lines in 56% and at least 4 lines in 28%. For ARTs, preoperative VA was 1.460 ± 0.391 logMAR. MHD was 390.2 ± 203.7 µm (range, 132-687 µm). All 5 ARTs (100%) resulted in MTMH closure. At postoperative month 6, VA was stable at 1.000 ± 0.246 logMAR (P = 0.08). Visual acuity improved at least 2 lines in 25%. CONCLUSIONS: Surgical closure of macular holes improved VA in 57% of MTMHs. Internal limiting membrane flaps achieved better anatomic and functional outcomes than ILM peeling alone. Autologous retinal transplantation may be an option for refractory MTMHs. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Updates on Emerging Interventions for Autosomal Recessive ABCA4-Associated Stargardt Disease.

Autosomal recessive Stargardt disease (STGD1) is an inherited retinal degenerative disease associated with a mutated ATP-binding cassette, subfamily A, member 4 (ABCA4) gene. STGD1 is the most common form of juvenile macular degeneration with onset in late childhood to early or middle adulthood and causes progressive, irreversible visual impairment and blindness. No effective treatment is currently available. In the present article, we review the most recent updates in clinical trials targeting the management of STGD1, including gene therapy, small molecule therapy, and stem cell therapy. In gene therapy, dual adeno-associated virus and non-viral vectors have been successful in delivering the human ABCA4 gene in preclinical studies. For pharmaceutical therapies ALK-001, deuterated vitamin A shows promise with preliminary data for phase 2 trial, demonstrating a decreased atrophy growth rate after two years. Stem cell therapy using human pluripotent stem cell-derived retinal pigment epithelium cells demonstrated long-term safety three years after implantation and visual acuity improvements in the first two years after initiation of therapy. Many other treatment options have ongoing investigations and clinical trials. While multiple potential interventions have shown promise in attenuating disease progression, further exploration is necessary to demonstrate treatment safety and efficacy.

Current Assistive Devices Usage and Recommendations for a Future Artificial Vision Prosthesis among Patients with Severe Visual Impairment Due to Inherited Retinal Diseases.

Patients with inherited retinal diseases (IRDs) utilize various adaptive techniques and devices designed to assist them with activities of daily living (ADLs). The purpose of this study was to assess the assistive devices used by patients with IRDs, the difficulties they face despite these devices, and their recommendations for a future visual prosthesis. In collaboration with blind patients, an online survey was developed and administered to adults with IRDs and visual acuities of 20/400 to no light perception in the better-seeing eye. We analyzed data from 121 survey respondents (aged 18 to >80 years). Five respondents were Argus II prosthesis recipients. The most commonly used aids were cellular phones/tablets for reading (63.6%) as well as a sighted guide (75.0%) and a cane (71.4%) for mobility. Despite current assistive devices, participants reported continued difficulty with ADLs. Improved navigation, reading, and facial recognition were ranked the most desirable features for future visual prostheses. Argus II recipients suggested technology with improved ability to recognize objects and obstacles, detect movement, and cut out busy backgrounds. These insights are valuable in shaping the design of future prosthetic devices tailored to the needs of IRD patients.

Bilateral exudative retinal detachments after subretinal gene therapy with voretigene neparvovec-rzyl for RPE65 Leber Congenital Amaurosis.

Purpose: To report panuveitis with exudative retinal detachments in a healthy 27-year-old woman with biallelic mutations in the RPE65 gene, who underwent bilateral sequential gene therapy with subretinal administration of voretigene neparvovec-rzyl. Observations: Visual acuity improved for 30 days after surgery as oral corticosteroids were tapered. At postoperative week 6, vision declined due to sudden onset uveitis and exudative retinal detachments in both eyes. HLA Class II typing revealed the haplotype associated with sympathetic ophthalmia and Vogt-Koyanagi-Harada (VKH). The inflammation improved after corticosteroid, mycophenolate mofetil, and adalimumab therapy while vision remained poor. Conclusions and Importance: Surgically-induced sympathetic ophthalmia is a plausible explanation for the clinical findings; surgery of both eyes within one week would conceal the inciting eye. VKH or inflammation related to the gene therapy are other possible etiologies but severe bilateral panuveitis has not been reported with voretigene neparvovec-rzyl. Informed consent for gene therapy surgery should include a discussion of the rare complication of sympathetic ophthalmia following vitrectomy surgery.

Surgical Observations From the First 120 Cases of Subretinal Gene Therapy for Inherited Retinal Diseases.

PURPOSE: To report surgical observations formulated during the first 120 cases of subretinal gene therapy in patients with inherited retinal degenerations (IRDs). METHODS: A two-surgeon team compiled surgical observations and formulated surgical pearls based on the consecutive cases of subretinal viral vector injection in patients enrolled in clinical trials focusing on choroideremia, achromatopsia, and RP GTPase regulator associated retinitis pigmentosa, as well as patients with retinal pigment epithelium-specific-65-kDa (RPE65) associated Leber congenital amaurosis receiving Food and Drug Administration-approved voretigene neparvovec-rzyl therapy. RESULTS: One hundred twenty subretinal surgeries were performed by a two-surgeon team. Key anatomical features pertinent to surgical management were noted and are described in this article. Surgical decision making for successful subretinal administration of viral vectors and management of potential surgical challenges were formulated. CONCLUSION: Lessons learned during subretinal gene therapy cases may be helpful to other surgeons entering clinical trials or performing postapproval gene therapy administration. Surgical pearls outlined in this article may also be helpful for other targeted subretinal therapies, such as cellular transplantation or retinal prosthesis implantation.

Needle aspiration for management of acute intraoperative fluid misdirection during phacoemulsification.

Purpose: Acute intraoperative fluid misdirection is a serious complication that may occur during phacoemulsification. We provide a detailed description and a video of our preferred technique for prompt management of acute intraoperative fluid misdirection. Observations: A 79-year-old male developed sudden shallowing of the anterior chamber and marked elevation of intraocular pressure at hydrodissection during phacoemulsification surgery. Treatment consisted of a needle aspiration of trapped fluid from the retrolental space, employing a 5/8th inch, 25-gauge needle on a medium-size syringe leading to immediate softening of the globe and deepening of the anterior chamber. The rest of the case proceeded uneventfully. The patient had uncomplicated recovery and final best-corrected visual acuity of 20/20. Conclusions and importance: Acute subcapsular infusion fluid entrapment may occur during uneventful phacoemulsification. Needle aspiration of retrolental fluid is a simple and inexpensive method for immediate resolution of high IOP and deepening of the anterior chamber, allowing the case to proceed.

Visual Acuity, Retinal Morphology, and Patients' Perceptions after Voretigene Neparovec-rzyl Therapy for RPE65-Associated Retinal Disease.

OBJECTIVE: To explore the effect of patients' age, baseline visual acuity (VA), and intraoperative foveal detachment on outcomes of subretinal voretigene neparvovec-rzyl (Luxturna) therapy and to assess patients' perceptions of the treatment effect. DESIGN: Multicenter, retrospective, consecutive case series, and cross-sectional prospective survey. PARTICIPANTS: All 41 consecutive patients treated with voretigene neparvovec-rzyl after Food and Drug Administration approval at 3 institutions between January 2018 and May 2020. METHODS: A retrospective chart review of operative reports, clinical notes, ancillary testing, and complications, comparing data at baseline and at 1, 2 to 3, 6 to 9, and 10 to 15 months after subretinal surgery was conducted. A survey was administered to adult patients and parents of pediatric patients. MAIN OUTCOME MEASURES: Changes in best-corrected VA and retinal morphology and in patients' perceptions. RESULTS: Seventy-seven eyes of 41 patients (16 adults and 25 pediatric patients; age range, 2-44 years; mean follow-up, 10 months [range, 1 week to 18.5 months]) were analyzed. There was no statistically significant vision change for the adults, whereas there was a trend of improvement for pediatric patients, which reached statistical significance for some time points. The baseline VA did not affect the posttherapy VA (P = 0.23). The central foveal thickness decreased mildly in both pediatric patients and adults, without significant differences between the populations. The fovea was detached by voretigene neparvovec-rzyl in 62 (81%) eyes. The inner segment-outer segment junction remained unchanged in 91% of 54 eyes with gradable OCT, with or without foveal detachment. Thirty-two (78%) patients were reached for the survey an average of 1.15 ± 0.50 years (range, 0.31 to 2.31) after the surgery in the first eye. Improvement in night, day, or color vision was reported by 23 (72%), 22 (69%), and 18 (56%) patients, respectively. CONCLUSIONS: This study is limited by the large variability in follow-up time. There were no persistent statistically significant vision changes. A decrease in foveal thickness was noted in most eyes, but the long-term significance of this remains to be determined.

Autologous Retinal Transplantation for Primary and Refractory Macular Holes and Macular Hole Retinal Detachments: The Global Consortium.

PURPOSE: To report the anatomic and functional outcomes of autologous retinal transplantation (ART). DESIGN: Multicenter, retrospective, interventional, consecutive case series. PARTICIPANTS: One hundred thirty eyes of 130 patients undergoing ART for the repair of primary and refractory macular holes (MHs), as well as combined MH-rhegmatogenous retinal detachment (MH-RRD), between January 2017 and December 2019. METHODS: All patients underwent pars plana vitrectomy and ART, with surgeon modification of intraoperative variables. A large array of preoperative, intraoperative, and postoperative data was collected. Two masked reviewers graded OCT images. Multivariate statistical analysis and subgroup analysis were performed. MAIN OUTCOME MEASURES: Macular hole closure rate, visual acuity (VA), external limiting membrane and ellipsoid zone (EZ) band integrity, and alignment of neurosensory layers (ANL) on OCT. RESULTS: One hundred thirty ART surgeries were performed by 33 vitreoretinal surgeons worldwide. Patient demographics were: mean age of 63 ± 6.3 years, 58% female, 41% White, 23% Black, 19% Asian, and 17% Latino. Preoperative VA was 1.37 ± 0.12 logarithm of the minimum angle of resolution (logMAR; Snellen equivalent, approximately 20/500), which improved significantly to 1.05 ± 0.09 logMAR (Snellen equivalent, approximately 20/225; P < 0.001) after surgery (mean follow-up, 8.6 ± 0.8 months). Autologous retinal transplantation was performed for primary MH repair in 27% of patients (n = 35), for refractory MH in 58% of patients (n = 76; mean number of previous surgeries, 1.6 ± 0.2), and for MH-RRD in 15% of patients (n = 19). Mean maximum MH diameter was 1470 ± 160 µm, mean minimum diameter was 840 ± 94 µm, and mean axial length was 24.6 ± 3.2 mm. Overall, 89% of MHs closed (78.5% complete; 10% small eccentric defect), with a 95% closure rate in MH-RRD (68.4% complete; 26.3% small eccentric defect). Visual acuity improved by at least 3 lines in 43% of eyes and by at least 5 lines in 29% of eyes. Reconstitution of the EZ (P = 0.02) and ANL (P = 0.01) on OCT were associated with better final VA. Five cases of ART graft dislocation (3.8%), 5 cases of postoperative retinal detachment (3.8%), and 1 case of endophthalmitis (0.77%) occurred. CONCLUSIONS: In this global experience, patients undergoing ART for large primary and refractory MHs and MH-RRDs achieved good anatomic and functional outcomes, with low complication rates despite complex surgical pathologic features.

Rhegmatogenous Retinal Detachment after Intravitreal Injection.

PURPOSE: To describe the clinical features and outcomes in patients with rhegmatogenous retinal detachment (RRD) after intravitreal injection of pharmacologic agents. DESIGN: Retrospecitve case series. PARTICIPANTS: Patients diagnosed with rhegmatogenous retinal detachment within 3 months of receiving an intravitreal injection of a pharmacologic agent for treatment of macular disease. METHODS: Retrospective case series of reported cases of RRD in patients with prior intravitreal injection who underwent subsequent surgical repair at a university referral center. MAIN OUTCOME MEASURES: Visual acuity (VA), single surgery anatomic success rate (SSAS) and retinal reattachment at last follow-up. RESULTS: Thirteen patients were identified to have RRD within 3 months of intravitreal injection. Injection was performed in the inferotemporal quadrant in 12 of 13 eyes (92%) with a 31- or 32-gauge needle. Additional risk factors for RRD other than intravitreal injection were present in 5 of 13 eyes (38%), including prior pars plana vitrectomy (3 eyes), history of retinal tear (1 eye), and history of RRD in the fellow eye (1 eye). Average duration from time of injection to diagnosis of RRD was 27 days (range, 5-43 days). Retinal reattachment was achieved in 12 of 13 eyes (92%). Visual acuity returned to baseline in only 3 of 13 eyes (23%) at the last follow-up visit. CONCLUSIONS: Although RRD after intravitreal injection is rare, prior retinal surgery and alternate risk factors for RRD may predispose to RRD after intravitreal injection. Surgical outcomes were generally favorable, but VA outcomes were limited by the high rate of macula-off RRD and the underlying macular disease.

Outcomes of Pars Plana Vitrectomy Alone versus Combined Scleral Buckling plus Pars Plana Vitrectomy for Primary Retinal Detachment.

PURPOSE: We compared the outcomes of primary uncomplicated rhegmatogenous retinal detachment (RRD) repair using pars plana vitrectomy (PPV) alone versus combined scleral buckling plus PPV (SB+PPV). DESIGN: Retrospective, observational study. PARTICIPANTS: Patients with primary RRD who underwent PPV or SB+PPV from June 1, 2014, through December 31, 2017. METHODS: We performed a single-institution, retrospective, observational study of 488 consecutive patients with primary RRD repaired via PPV alone or SB+PPV and gas tamponade. We excluded patients younger than 18 years and those with advanced proliferative vitreoretinopathy, giant retinal tear, trauma, or secondary forms of RRD. We performed logistic regression and Cox proportional hazard regression analyses to identify potential risk factors associated with a retinal redetachment. MAIN OUTCOME MEASURES: Single-operation anatomic success (SOAS), defined as adequate retinal reattachment achieved with only 1 procedure. RESULTS: The mean follow-up interval was 14.3 months. Single-operation anatomic success and final anatomic success were achieved in 425 eyes (87.1%) and 487 eyes (99.8%), respectively. Single-operation anatomic success was achieved in 90 of 111 eyes (81.1%) with PPV alone compared with 345 of 374 eyes (92.2%) with SB+PPV (P = 0.0010). Scleral buckling plus PPV showed greater SOAS than PPV alone in phakic eyes (P < 0.0001), but not in eyes with a posterior chamber intraocular lens (PCIOL). Retinal redetachments occurred on average at 1.5 and 9 months after the initial surgery. Significant best-corrected visual acuity improvement was associated with SOAS (P < 0.0001). CONCLUSIONS: Scleral buckling plus PPV resulted in greater SOAS outcomes than PPV alone for primary RRD repair. Phakic eyes achieved greater surgical success with SB+PPV, whereas eyes with a PCIOL achieved similar results with both methods. Most retinal redetachments occurred within the initial postoperative 3-month period. Single-operation anatomic success was associated with statistically significant visual improvement.

Initial results from a first-in-human gene therapy trial on X-linked retinitis pigmentosa caused by mutations in RPGR.

Retinal gene therapy has shown great promise in treating retinitis pigmentosa (RP), a primary photoreceptor degeneration that leads to severe sight loss in young people. In the present study, we report the first-in-human phase 1/2, dose-escalation clinical trial for X-linked RP caused by mutations in the RP GTPase regulator (RPGR) gene in 18 patients over up to 6 months of follow-up (https://clinicaltrials.gov/: NCT03116113). The primary outcome of the study was safety, and secondary outcomes included visual acuity, microperimetry and central retinal thickness. Apart from steroid-responsive subretinal inflammation in patients at the higher doses, there were no notable safety concerns after subretinal delivery of an adeno-associated viral vector encoding codon-optimized human RPGR (AAV8-coRPGR), meeting the pre-specified primary endpoint. Visual field improvements beginning at 1 month and maintained to the last point of follow-up were observed in six patients.

ADVERSE EVENTS OF THE ARGUS II RETINAL PROSTHESIS: Incidence, Causes, and Best Practices for Managing and Preventing Conjunctival Erosion.

PURPOSE: To analyze and provide an overview of the incidence, management, and prevention of conjunctival erosion in Argus II clinical trial subjects and postapproval patients. METHODS: This retrospective analysis followed the results of 274 patients treated with the Argus II Retinal Prosthesis System between June 2007 and November 2017, including 30 subjects from the US and European clinical trials, and 244 patients in the postapproval phase. Results were gathered for incidence of a serious adverse event, incidence of conjunctival erosion, occurrence sites, rates of erosion, and erosion timing. RESULTS: Overall, 60% of subjects in the clinical trial subjects versus 83% of patients in the postapproval phase did not experience device- or surgery-related serious adverse events. In the postapproval phase, conjunctival erosion had an incidence rate of 6.2% over 5 years and 11 months. In 55% of conjunctival erosion cases, erosion occurred in the inferotemporal quadrant, 25% in the superotemporal quadrant, and 20% in both. Sixty percent of the erosion events occurred in the first 15 months after implantation, and 85% within the first 2.5 years. CONCLUSION: Reducing occurrence of conjunctival erosion in patients with the Argus II Retinal Prosthesis requires identification and minimization of risk factors before and during implantation. Implementing inverted sutures at the implant tabs, use of graft material at these locations as well as Mersilene rather than nylon sutures, and accurate Tenon's and conjunctiva closure are recommended for consideration in all patients.