Gene therapy for neovascular age-related macular degeneration by subretinal delivery of RGX-314: a phase 1/2a dose-escalation study.

BACKGROUND: Frequent anti-vascular endothelial growth factor A (VEGF-A) injections reduce the risk of rapid and severe vision loss in patients with neovascular age-related macular degeneration (nAMD); however, due to undertreatment, many patients lose vision over time. New treatments that provide sustained suppression of VEGF-A are needed. RGX-314 (currently known as ABBV-RGX-314) is an adeno-associated virus serotype 8 vector that expresses an anti-VEGF-A antigen-binding fragment, which provides potential for continuous VEGF-A suppression after a single subretinal injection. We report results on the safety and efficacy of subretinal injection of RGX-314 in patients with nAMD. METHODS: For this open-label, multiple-cohort, multicentre, phase 1/2a, dose-escalation study conducted at eight sites in the USA, we enrolled participants with nAMD aged 50-89 years who had previously been treated with anti-VEGF injections into five cohorts (with five different doses of RGX-314). To be eligible, participants had to have macular neovascularisation secondary to nAMD with subretinal or intraretinal fluid in the centre subfield, be pseudophakic (after cataract removal), and have a best-corrected visual acuity (BCVA) in the study eye between 20/63 and 20/400 for the first participant in each cohort and between 20/40 and 20/400 for others. Subretinal injection of RGX-314 was done without a pre-bleb by a wet-laboratory-trained vitreoretinal surgeon. Cohort 1 received 3 × 109 genome copies per eye, cohort 2 received 1 × 1010, and cohort 3 received 6 × 1010. Two additional dose cohorts (cohort 4: 1·6 × 1011; cohort 5: 2·5 × 1011) were added. Participants were seen 1 day and 1 week after administration of RGX-314, and then monthly for 2 years (up to week 106). The primary outcome was safety of RGX-314 delivered by subretinal injection up to week 26. This analysis includes all 42 patients enrolled in the study. This study is registered with ClinicalTrials.gov, NCT03066258. FINDINGS: Between May 12, 2017, and May 21, 2019, we screened 110 patients for eligibility and enrolled 68. 42 participants demonstrated the required anatomic response to intravitreal ranibizumab and then received a single RGX-314 injection (dose range 3 × 109 to 2·5 × 1011 genome copies per eye) and were followed up for 2 years. There were 20 serious adverse events in 13 participants, of which one was possibly related to RGX-314: pigmentary changes in the macula with severe vision reduction 12 months after injection of RGX-314 at a dose of 2·5 × 1011 genome copies per eye. Asymptomatic pigmentary changes were seen in the inferior retinal periphery several months after subretinal injection of RGX-314 most commonly at doses of 6 × 1010 genome copies per eye or higher. There were no clinically determined immune responses or inflammation beyond that expected following routine vitrectomy. Doses of 6 × 1010 genome copies or higher resulted in sustained concentrations of RGX-314 protein in aqueous humour and stable or improved BCVA and central retinal thickness with few or no supplemental anti-VEGF-A injections in most participants. INTERPRETATION: Subretinal delivery of RGX-314 was generally well tolerated with no clinically recognised immune responses. RGX-314 gene therapy provides a novel approach for sustained VEGF-A suppression in patients with nAMD that has potential to control exudation, maintain vision, and reduce treatment burden after a single administration. Results from this study informed the pivotal programme to evaluate RGX-314 in patients with nAMD. FUNDING: RegenxBio.

Enhanced durability and evolution of retreatment criteria of intravitreal antivascular endothelial growth factor agents for diabetic macular edema.

PURPOSE OF REVIEW: The increasing prevalence of diabetic macular edema (DME) necessitates an updated review of treatment modalities. While the shift from laser to anti-vascular endothelial growth factor (anti-VEGF) therapy has transformed patient outcomes, benefits of these agents are not fully realized in real-world implementation relative to the setting of controlled clinical trials. This review outlines the evolution of intravitreal anti-VEGF treatment extension protocols for DME that reflect efforts to address treatment adherence challenges while optimizing visual outcomes. RECENT FINDINGS: Recent studies highlight the efficacy of extended-interval dosing with anti-VEGF agents in managing DME. Trials such as RISE/RIDE, VISTA/VIVID, and LUCIDATE have established the foundation of these regimens by demonstrating sustained visual gains with continuous treatment. However, newer trials including PROTOCOL T, KESTREL/KITE, YOSEMITE/RHINE, and PHOTON have furthered this concept, revealing that less frequent dosing of various anti-VEGF agents can maintain similar visual acuity and anatomical outcomes to traditional monthly injections. SUMMARY: The reviewed findings suggest a paradigm shift in DME treatment toward less frequent anti-VEGF injections. This has significant implications for clinical practice, potentially leading to greater adherence to treatment regimens and sustained visual function in patients, while minimizing treatment burden and healthcare costs. Further investigation into the long-term effects of extended dosing intervals is required.

Patient Accessibility to Eye Care in the United States.

PURPOSE: The United States (US) federal government uses health provider shortage areas (HPSAs) to define patient accessibility to primary care physicians. It is unclear whether HPSAs can be applied to eye care providers (ECPs). Our study determined the applicability of federal HPSA designations to ECP availability in the US. DESIGN: Cross-sectional study. PARTICIPANTS: US general population and ophthalmologists/optometrists in the Medicare database. METHODS: The primary care HPSA score, visual impairment prevalence, and ECP location were determined for each census tract or county using data from the US Department of Health and Human Services, the Centers for Disease Control and Prevention, and Centers for Medicare and Medicaid Services. MAIN OUTCOME MEASURES: Association of HPSA with vision loss and ECP density was examined. The 2-step floating catchment area approach was used to newly define eye care shortage areas (patient accessibility score [PAS], higher being worse accessibility) for every county in the US, by weighting the 2-step FCA scores by prevalence of vision loss and ECP density. Multivariable logistic regression was used to identify sociodemographic variables associated with areas of ECP shortage. RESULTS: Among 72 735 census tracts included, statistically significant but weak correlations of HPSA score with visual impairment (VI) (r = 0.38; P < 0.0001) and ECP density per county population (r = -0.18; P < 0.0001) were found. Only 54.0% of census tracts with < 25th percentile ECP density per county were HPSAs (P < 0.0001). Of census tracts > than 75th percentile for VI only 58.0% were HPSAs (P < 0.0001). Multivariable regression found a higher odds of ECP PAS ≥ 75th percentile (worse accessibility) in rural counties (adjusted odds ratio [aOR], 2.47; 95% confidence interval [CI], 1.93-3.67; P < 0.001) and counties with a greater prevalence of residents with less than a high school education (aOR, 1.21; 95% CI, 1.19-1.25; P < 0.001), residents ≥ 65 years of age (aOR, 1.10; 95% CI, 1.07-1.13; P < 0.001), and uninsured residents (aOR, 1.04; 95% CI, 1.01-1.06; P < 0.001). Counties with a greater proportion of men (aOR, 0.93; 95% CI, 0.89-0.967; P < 0.001) or White residents (aOR, 0.99; 95% CI, 0.98-0.99) had a lower odds of ECP PAS ≥ 75th percentile. CONCLUSIONS: Current HPSAs only weakly correlate with ECP supply. We propose a new approach to identify counties with high need but limited access to eye care. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Recent advances in the management of proliferative diabetic retinopathy.

PURPOSE OF REVIEW: The prevalence of diabetic retinopathy continues to rise. This review highlights advances in imaging, medical, and surgical management of proliferative diabetic retinopathy (PDR) in recent years. RECENT FINDINGS: Ultra-widefield fluorescein angiography has been shown to better characterize which patients have predominantly peripheral lesions and who may advance to more advanced forms of diabetic retinopathy. This was well demonstrated in DRCR Retina Network's Protocol AA. Protocol S demonstrated that antivascular endothelial growth factor (VEGF) treatment alone can be useful in the management of select PDR patients - particularly those without high-risk features. However, a growing body of literature highlights how lapse in care is a significant concern in PDR patients, and tailoring one's approach to treatment based on patient needs is recommended. In patients with high-risk features or where there is concern for lost-to-follow-up, incorporation of panretinal photocoagulation in the treatment paradigm is recommended. Protocol AB highlighted how patients with more advanced disease may benefit from earlier surgical intervention for earlier visual recovery but that continued anti-VEGF treatment may result in similar visual outcomes over a longer period. Finally, earlier surgical intervention for PDR without vitreous hemorrhage (VH) or retinal detachment is being considered a potential option to minimize treatment burden. SUMMARY: Recent advances in imaging, as well as medical and surgical treatment options for PDR, have provided a deeper understanding of PDR management, which can be optimized for the individual patient.

Endophthalmitis following cataract surgery: visual outcomes, microbial spectrum and complications.

PURPOSE OF REVIEW: The aim of this study was to update visual outcomes, microbial spectrum and complications in eyes with endophthalmitis following cataract surgery. RECENT FINDINGS: A single-institution, retrospective review of eyes treated for endophthalmitis following cataract surgery between 2 January 2014 and 10 January 2017. This study included 112 cases of endophthalmitis following cataract surgery, 58 of which were culture-positive (51.8%). The most isolated organisms were coagulase-negative Staphylococci (56.9%). Oral flora were present in 17.2% of cases. At 6 months, 71.7% of patients achieved visual acuity of at least 20/200 and 51.7% achieved at least 20/40 or better. Visual acuity was better in culture-negative vs. culture-positive cases (∼20/290 vs. ∼20/80, P   =  0.03), and in nonoral flora-associated vs. oral flora-associated culture-positive cases (∼CF vs. ∼20/150, P   <  0.01). SUMMARY: Following postcataract surgery endophthalmitis, approximately 70% of eyes achieved vision of 20/200 or better and half achieved vision of 20/40 or better 6 months after treatment. Poor visual outcomes were seen in eyes with positive bacterial cultures and with oral flora.

EPIRETINAL MEMBRANE WITH FOVEAL HERNIATION: Visual and Surgical Outcomes.

PURPOSE: Foveal herniation occurs when neuroretinal tissue protrudes through and above the level of an epiretinal membrane. This study describes the visual symptoms and spectral domain optical coherence tomography findings associated with foveal herniation and evaluates the postoperative visual, anatomical, and surgical outcomes. METHODS: A multicenter retrospective review of patients diagnosed with epiretinal membrane identified 59 patients with preoperative foveal herniation on spectral domain optical coherence tomography. Data regarding visual symptoms, preoperative and postoperative best-corrected visual acuity (BCVA), central retinal thickness, macular volume, and size of foveal herniation were collected, and statistical analysis was performed. RESULTS: A total of 58 of the 59 patients with foveal herniation underwent surgical epiretinal membrane peeling, with foveal contour restored in 53.5% of patients after surgery. Average BCVA improved from 20/80 to 20/40 Snellen equivalent at most-recent postoperative visit (P < 0.0001). The average central retinal thickness decreased from 632 µm to 432 µm (P < 0.0001) and the average macular volume decreased from 11.3 mm3 to 9.5 mm3 (P < 0.0001) at 3 months postoperatively. Preoperatively, greater herniation height was associated with worse BCVA (P = 0.008), greater central retinal thickness (P = 0.01), retinoschisis, cystoid macular edema, foveolar detachment, ellipsoid zone abnormality, and external limiting membrane abnormalities (P < 0.05). Postoperatively, there was a decrease in retinoschisis, cystoid macular edema, foveolar detachment, ellipsoid zone, and external limiting membrane abnormality (P < 0.05) on spectral domain optical coherence tomography. CONCLUSION: Patients with larger foveal herniation height had greater preoperative central retinal thickness, worse preoperative and postoperative BCVA, and more intraretinal abnormalities on spectral domain optical coherence tomography. Surgical epiretinal membrane peeling in patients with foveal herniation resulted in a significant improvement in patients' BCVA and microstructural abnormalities.

VITRECTOMY FOR VITREOUS HEMORRHAGE ASSOCIATED WITH RETINAL VEIN OCCLUSION: Visual Outcomes, Prognostic Factors, and Sequelae.

PURPOSE: To report the outcomes of pars plana vitrectomy for vitreous hemorrhage (VH) associated with retinal vein occlusion and to identify prognostic indicators. METHODS: Interventional, retrospective consecutive case series between 2015 and 2021. RESULTS: The study included 138 eyes of 138 patients (64 female and 74 male); 81 patients had branch retinal vein occlusion and 57 had central retinal vein occlusion. The mean age was 69.8 years. The mean duration between the diagnosis of VH and surgery was 79.6 ± 115.3 (range, 1-572) days. The mean follow-up was 27.2 months. The logarithm of the minimum angle of resolution visual acuity significantly improved from 1.95 ± 0.72 (Snellen equivalent, 20/1782) to 0.99 ± 0.87 (20/195) at 6 months and to 1.06 ± 0.96 (20/230) at the final visit (both P < 0.001). The visual acuity at 6 months improved by three or more lines in 103 eyes (75%). Postoperative complications during follow-up included recurrent VH in 16 eyes (12%) (of which 8 eyes underwent reoperations), rhegmatogenous retinal detachment in six eyes (4%), and new neovascular glaucoma in three eyes (2%). Worse final visual acuity was significantly associated with older age ( P = 0.007), concurrent neovascular glaucoma ( P < 0.001), central retinal vein occlusion ( P < 0.001), worse preoperative visual acuity ( P < 0.001), postoperative new neovascular glaucoma ( P = 0.021), and postoperative retinal detachment ( P < 0.001). The duration of VH was not associated with visual outcomes ( P = 0.684). Preoperative antivascular endothelial growth factor injections and tamponade did not prevent postoperative recurrent VH. CONCLUSION: Pars plana vitrectomy is effective for VH associated with retinal vein occlusion, regardless of the duration of hemorrhage. However, pre-existing risk factors and postoperative sequelae may limit visual recovery.

Indications for surgical management of retained lens fragments.

PURPOSE OF REVIEW: Retained lens fragments are a relatively rare occurrence after cataract surgery. While no definite guidelines for the surgical management or timing of surgery of this complication exist, surgery is indicated for patients with large lens fragments, persistent inflammation, secondary glaucoma, corneal edema, retinal tears or detachments, and associated endophthalmitis. The aim of this review is to summarize the current surgical management of retained lens material. RECENT FINDINGS: The Intelligent Research in Sight registry database of 2.26 million patients who underwent cataract surgery in the US indicated that 0.18% (1 in 563) had secondary removal of retained lens fragments in the anterior chamber in the operating room within 1 year of the original cataract surgery. The risk of returning to the operating room for retained lens material removal was greater among men, smokers, patients with Medicaid or military insurance, and those who had complex cataract surgery. Medical management with topical corticosteroids or observation may be considered for small lens fragments, but surgical removal remains the mainstay of the treatment for large lens fragments. SUMMARY: Retained lens fragments following cataract surgery may result in various vision-threatening complications. Understanding the risk factors, diagnosis, and surgical management of retained lens fragments are critical to preserving good visual outcomes. Vitrectomy is effective in patients with posterior nuclear fragments, retinal detachment, endophthalmitis, or uncontrolled glaucoma not responding to medical management. The best timing for surgery for retained lens fragments should be further investigated in a prospective study.

Pilocarpine 1.25% and the changing landscape of presbyopia treatment.

PURPOSE OF REVIEW: Despite affecting approximately 1.8 billion individuals worldwide, until recently, a pharmacologic treatment for presbyopia was not available. This special commentary reviews the treatment of presbyopia with a focus on the recently approved medication Vuity (pilocarpine 1.25%, Allergan, an AbbVie Company). RECENT FINDINGS: Vuity is a re-engineered formulation of pilocarpine 1.25% specifically designed for the treatment of presbyopia. Recently published results from the GEMINI 1 Phase 3 clinical trial reported improvement in distance corrected near vision without significant compromise in distance vision. No unexpected safety findings were reported with mild headache being the most common adverse event. Notably, there were no reported cases of retinal detachment or angle closure during the 30-day phase 3 clinical trials. SUMMARY: Vuity is the first treatment designed and FDA approved to treat the growing presbyopia market. Phase 3 clinical trials demonstrated its ability to improve near vision without significant compromise in distance vision. We recognize this paradigm shift in the treatment of presbyopia and anxiously await additional treatment options for this ubiquitous condition.

Stellate nonhereditary idiopathic foveomacular retinoschisis and an approach to the differential diagnosis of macular star.

PURPOSE OF REVIEW: This review aims to introduce stellate nonhereditary idiopathic foveomacular retinoschisis (SNIFR) and its differential diagnosis. We summarize findings from case reports and series published in the last few years on the clinical and imaging findings in SNIFR. RECENT FINDINGS: SNIFR presents as either a unilateral or bilateral macular star on fundus examination without clinical or imaging evidence of exudation or frank vitreomacular traction. optical coherence tomography (OCT) imaging shows schisis cavities in the Henle fibre and outer plexiform layers that correspond to the stellate en face findings. Visual acuity is usually minimally affected, and the presence of significant vision loss should prompt high clinical suspicion for alternate diagnoses. SUMMARY: SNIFR is a recently characterized clinical entity that serves as an important addition to the differential diagnosis of a macular star. It is a diagnosis of exclusion and should be distinguished from other causes of macular star such as neuroretinitis, vitreomacular traction, ocular manifestations of malignant hypertension, congenital juvenile X-linked macular schisis, myopic maculopathy, optic pit maculopathy, nicotinic acid maculopathy or taxane maculopathy among others.

REFRACTIVE ERROR CHANGE DURING TREATMENT OF DIABETIC MACULAR EDEMA: A Post Hoc Analysis of the Diabetic Retinopathy Clinical Research Protocol T Trial.

PURPOSE: To evaluate the impact of anti-vascular endothelial growth factor therapy on the refractive error in eyes with diabetic macular edema. METHODS: Post hoc analysis of Diabetic Retinopathy Clinical Research protocol T. Spherical equivalent (SE) was calculated for study and fellow eyes at baseline, 1-year, and 2-year visits. The SE change of the eyes with edema was compared with those with resolved edema. The correlation between refractive error changes and central subfield thickness was evaluated. RESULTS: Among 543 study eyes, SE changed from -0.17 (2.04) D at baseline visit to -0.16 (2.14) D at 2 years giving a hyperopic shift of 0.04 (0.82) D (P = 0.022). Among fellow eyes, mean (SD) SE changed from -0.19 (2.1) D at baseline to -0.11 (2.1) D at 2 years, giving a hyperopic shift of 0.12 (0.84) D (P = 0.001). No significant difference in SE shift was found between eyes with and without edema at 2 years in phakic (0.12D and 0.08 D, P = 0.87) and pseudophakic eyes (-0.24D and -0.08D, P = 0.30). The SE shift was not correlated with central subfield thickness change at the end of the second year (r = 0.02, P = 0.62). CONCLUSION: Diabetic macular edema patients have minimal changes in refractive error. The correction of refractive error may be considered during treatment, regardless of the presence of edema.

FACTORS AFFECTING RETINAL REDETACHMENT AFTER SILICONE OIL REMOVAL FOR RHEGMATOGENOUS RETINAL DETACHMENTS.

PURPOSE: To report factors affecting the retinal redetachment rate after silicone oil removal (SOR) following rhegmatogenous retinal detachment (RRD) repair. METHODS: Retrospective cohort study from December 1, 2014, to March 1, 2020, of 205 consecutive patients treated for RRD with silicone oil (SO) tamponade and subsequent SOR with at least 6-month follow-up. Primary outcome measure was the rate of retinal redetachment after SOR. RESULTS: The retinal redetachment rate after SOR was 18.5%. Preoperative macula and lens status, proliferative vitreoretinopathy, previous retinectomy, retinal detachment size, concomitant phacoemulsification, previous scleral buckling, and endolaser during SOR did not affect the redetachment rate after SOR. Previous SO exchange was associated with increased redetachment (OR 2.53, 95% CI [1.11-5.80], P = 0.0278). Twelve months of SO tamponade had lower redetachment rates compared with 3 months (OR 0.25, 95% CI [0.04-0.09], P = 0.048). Shorter SO tamponade (3 vs. 12 months) had better final visual outcomes after SOR (0.80 ± 0.61 vs. 1.41 ± 0.66, P < 0.0001). CONCLUSION: No preoperative or intraoperative factors in this analysis influenced the risk of redetachment after SOR except duration of SO tamponade and previous SO exchange. Although longer SO tamponade duration may be associated with lower rates of redetachment, visual outcomes may be worse.

PREVALENCE, CHARACTERISTICS, AND OUTCOMES OF RHEGMATOGENOUS RETINAL DETACHMENT IN EYES WITH TRABECULECTOMY OR GLAUCOMA DRAINAGE DEVICES.

PURPOSE: To describe the prevalence, management, and outcomes of rhegmatogenous retinal detachment (RRD) after incisional glaucoma filtering surgery. METHODS: All patients with a history of trabeculectomy or glaucoma drainage device surgery who were subsequently diagnosed with an RRD from January 1, 2016, to January 1, 2021, at the Wills Eye Hospital were identified. RESULTS: Forty-six eyes met the inclusion criteria. The mean age was 60.7 ± 19.6 years, and 15 patients (32.6%) were female. Of all eyes, 34 (73.9%) were diagnosed with primary open-angle glaucoma. The mean time from most recent incisional glaucoma surgery to RRD diagnosis was 1,133 ± 1,644 days. There were 19 eyes (41.3%) with preoperative proliferative vitreoretinopathy (9 eyes [19.6%] with Grade C proliferative vitreoretinopathy) and 35 eyes (76.1%) had macula-off RRD at the time of presentation. At RRD presentation, 4 eyes (8.7%) had concomitant endophthalmitis, 5 (10.9%) had concurrent choroidal detachment, and 2 (4.7%) had concurrent vitreous hemorrhage. Primary vitrectomy was performed in most (91.3%) cases. Silicone oil tamponade was often required (71.1%). The single surgery success rate was 65.2% (30 of 46). The mean preoperative logarithm of the minimum angle of resolution visual acuity was 1.72 ± 0.78 (Snellen acuity 20/1,050), and the mean final postoperative logarithm of the minimum angle of resolution was 1.59 ± 0.89 (20/778, P = 0.2853). Of glaucoma surgeries performed, the 5-year prevalence of RRD was 0.71% (26 of 3,664, 95% Poisson confidence interval 0.48%-1.04%). CONCLUSION: The 5-year prevalence of RRDs after trabeculectomy or glaucoma drainage device was 0.71%. Most patients presented with macula-involving detachments, often with proliferative vitreoretinopathy. Anatomical and visual outcomes were poor.

Clinical Presentation of Rhegmatogenous Retinal Detachment during the COVID-19 Pandemic: A Historical Cohort Study.

PURPOSE: To investigate the effect of the coronavirus disease 2019 (COVID-19) pandemic on the clinical presentation of acute, primary rhegmatogenous retinal detachment (RRD). DESIGN: Single-center, consecutive case series with historical controls. PARTICIPANTS: Consecutive patients seeking treatment for primary RRD in a 50-day period during the COVID-19 pandemic (March 9-April 27, 2020) and the corresponding 50-day period during the previous year (March 4-April 22, 2019) in the United States. METHODS: The cohorts were compared to assess demographic variables and clinical presentations. Multivariate logistic regression was used to identify factors predictive of presenting macular attachment status. MAIN OUTCOME MEASURES: The primary outcome was the proportion of patients with macula-on RRD at presentation. Secondary outcomes included visual acuity (VA), duration of symptoms before presentation, proportion seeking treatment within 1 day of symptom onset, and presence of primary proliferative vitreoretinopathy (PVR). RESULTS: Eighty-two patients were included in the 2020 cohort compared with 111 patients in the 2019 primary control cohort. Demographic factors were similar between the groups. Significantly fewer patients demonstrated macula-on RRD in the 2020 cohort (20/82 patients [24.4%]) than in the 2019 cohort (55/111 patients [49.5%]; P = 0.001). Patients in the 2020 cohort showed worse median VA at presentation (1.00 logarithm of the minimum angle of resolution [logMAR; Snellen equivalent, 20/200] in 2020 vs. 0.48 logMAR [Snellen equivalent, 20/60] in 2019; P = 0.008), fewer patients sought treatment within 1 day of symptoms (16/80 patients [19.5%] in 2020 vs. 41/106 patients [36.9%] in 2019; P = 0.005), and a greater proportion demonstrated primary PVR (11/82 patients [13.4%] in 2020 vs. 5/111 patients [4.5%] in 2019; P = 0.03). In multivariate analysis, younger age (P = 0.03) and established patient status (P = 0.02) were independent predictors of macula-on status in the 2020 cohort. CONCLUSIONS: Patients with primary RRD during the 2020 COVID-19 pandemic were less likely to have macula-on disease and more likely to delay seeking treatment and to show worse vision and PVR.

Recent advances in diagnosis and management of sympathetic ophthalmia.

PURPOSE OF REVIEW: Sympathetic ophthalmia is a bilateral granulomatous uveitis that occurs following unilateral trauma or surgery and is sight-threatening in the contralateral eye. Despite significant potential morbidity, disease remains poorly understood. Variable presentations and clinical courses, as well as a lack of definitive diagnostic laboratory tests can complicate the diagnosis and result in delayed treatment, which can beget permanent vision loss. This review focuses on recent advances in areas of pathophysiology, classification, diagnosis and treatment. RECENT FINDINGS: Sympathetic ophthalmia is thought to involve a cell-mediated immune response to retinal and uveal antigens exposed through trauma or surgery. Multiple mechanisms have been implicated, including activation of the interleukin-23/IL-17 pathway. Ongoing emphasis is placed on early disease recognition and prompt treatment with multimodal imaging. Multiple authors advocate for the routine use of optical coherence tomography (OCT) for screening and disease monitoring. Systemic steroids and steroids sparing-immunosuppressive agents remain the mainstay of treatment. SUMMARY: Understanding pathophysiology may provide useful targets for drug development, as well as allow for identification of patients at risk. OCT is a useful tool in early diagnosis and management of sympathetic ophthalmia, as OCT changes may precede clinical symptoms and signs, allowing for early disease detection and better visual outcomes.

Endophthalmitis after cataract surgery: an update on recent advances.

PURPOSE OF REVIEW: Prevention and management of postcataract endophthalmitis remain quite relevant for anterior segment and vitreoretinal surgeons. Although the Endophthalmitis Vitrectomy Study, published in 1996, remains the only level 1 evidence for the management of postcataract endophthalmitis, recent advances have resulted in an evolution of practice patterns. The aim of this review is to summarize the literature regarding postcataract endophthalmitis with a focus on the last 18 months. RECENT FINDINGS: The IRIS registry indicates the rates of endophthalmitis are decreasing in the United States, and the outcomes appear to be improving. Intracameral moxifloxacin has become more widely accepted and intracameral vancomycin has been shown to be associated with retinal vasculitis. The role of systemic antibiotics and vitrectomy is unclear and practice patterns vary widely. SUMMARY: Although practice patterns vary, prevention and treatment of endophthalmitis after cataract surgery continues to improve. More uniform guidelines regarding surgical and medical therapy are necessary but the standard of prompt referral to a vitreoretinal specialist for immediate intravitreal antibiotics remains the most important intervention in the management of postcataract endophthalmitis.

Systemic considerations with pigmented fundus lesions and retinal pigment epithelium hamartomas in Turcot syndrome.

PURPOSE OF REVIEW: To illustrate retinal pigment epithelium hamartomas (RPEHs) in a patient with known Turcot syndrome and to demonstrate the significance of these lesions in other colonic polyposis syndromes. RECENT FINDINGS: The presence of multiple, bilateral RPEHs is a specific marker for familial adenomatous polyposis (FAP). Recent studies have noted RPEHs in associated syndromes including Gardner and Turcot syndromes. Herein, we illustrate an 18-year-old male patient with known brain medulloblastoma who was documented 7 years later to have asymptomatic RPEHs in both eyes, demonstrating hypo-autofluorescence. SUMMARY: This patient with previous medulloblastoma and known Turcot syndrome was later found to have typical RPEHs, a feature that is important in family screening. Confirmation of RPEHs related to Turcot syndrome was made, and genetic evaluation confirmed germline mutation in the adenomatous polyposis coli (APC) gene. Observation was advised. Due to the fairly rapid progression to colorectal cancer if untreated, ophthalmologists should be aware that RPEHs can be the first extracolonic manifestation of FAP, Gardner syndrome, and Turcot syndrome.

Ocular trauma during COVID-19 stay-at-home orders: a comparative cohort study.

PURPOSE OF REVIEW: The aim of this study was to report characteristics of patients presenting with serious ocular injuries during the COVID-19 stay-at-home orders. RECENT FINDINGS: Of 1058 patients presenting for emergency evaluation during the stay-at-home order, 62 (5.9%) patients [mean (SD) age, 41.1 (19.2) years; 19 (31%) women; 31 (50%) white] presented with severe ocular trauma. The daily mean (SD) number of patients who presented for emergency evaluation decreased from 49.0 (9) to 36.4 (6) during the quarantine (P < 0.001). Patients presenting during the stay-at-home order were less likely to have health insurance [odds ratio (OR), 0.33; 95% confidence interval (95% CI), 0.13-0.90, P = 0.024], more likely to have a delayed presentation (difference, 22.7 h, 95% CI, 5.8-39.5, P < 0.001, more likely to travel farther to seek emergency care (difference, 10.4 miles, 95% CI, 2.6-18.2, P < 0.001) and more likely to have an injury occur at home (OR, 22.8; 95% CI, 9.6-54.2, P < 0.001). Of injuries occurring at home, there was a significant increase in injuries arising from home improvement projects during the stay-at-home order (28 vs. 0%, P = 0.02). SUMMARY: During the COVID-19 pandemic, patients with ocular trauma were more likely to have injuries sustained at home and have additional barriers to care. These changes underscore a need for targeted interventions to optimize emergent eye care during a pandemic.

Age-related macular degeneration therapy: a review.

PURPOSE OF REVIEW: The purpose of this review is to describe the current clinical landscape of potential future therapies for both nonexudative (dry) and exudative (wet) age-related macular degeneration (AMD). We highlight some of the more promising treatments that are furthest along in development. RECENT FINDINGS: Patients with dry AMD have long been hoping for a highly efficacious treatment that may slow disease progression or even help regain vision. Patients with wet AMD have many effective treatment options but still there are those who have suboptimal responses or are burdened by the high frequency of treatment. We detail exciting new concepts and targets for novel medications. Specifically, for dry AMD we discuss research looking at complement inhibition, neuroprotection, visual cycle modulators, cell-based therapies, and anti-inflammatory agents. For wet AMD we summarize new, potentially more durable anti-vascular endothelial growth factor agents, extended release options, and gene therapy. SUMMARY: There are promising new strategies for AMD. Many of the potential new treatments are in or have recently completed phase 2 or phase 3 clinical trials with promising results thus far, including some that have received US Food and Drug Administration approval. Additional therapeutic breakthroughs will likely continue to occur thanks to the number of clinical trials that are nearing the finish line.