Retinal disorders such as retinitis pigmentosa, age-related retinal degeneration, oxygen-induced retinopathy, and ischemia-reperfusion injury cause debilitating and irreversible vision loss. While the exact mechanisms underlying these conditions remain unclear, there has been a growing body of evidence demonstrating the pathological contributions of oxidative stress across different cell types within the eye. Nuclear factor erythroid-2-related factor (Nrf2), a transcriptional activator of antioxidative genes, and its regulator Kelch-like ECH-associated protein 1 (Keap1) have emerged as promising therapeutic targets. The purpose of this review is to understand the protective role of the Nrf2-Keap1 pathway in different retinal tissues and shed light on the complex mechanisms underlying these processes. In the photoreceptors, we highlight that Nrf2 preserves their survival and function by maintaining oxidation homeostasis. In the retinal pigment epithelium, Nrf2 similarly plays a critical role in oxidative stabilization but also maintains mitochondrial motility and autophagy-related lipid metabolic processes. In endothelial cells, Nrf2 seems to promote proper vascularization and revascularization through concurrent activation of antioxidative and angiogenic factors as well as inhibition of inflammatory cytokines. Finally, Nrf2 protects retinal ganglion cells against apoptotic cell death. Importantly, we show that Nrf2-mediated protection of the various retinal tissues corresponds to a preservation of functional vision. Altogether, this review underscores the potential of the Nrf2-Keap1 pathway as a powerful tool against retinal degeneration. Key insights into this elegant oxidative defense mechanism may ultimately pave the path toward a universal therapy for various inherited and environmental retinal disorders.

One of the defining features of the retina is the tight metabolic coupling between cells such as photoreceptors and the retinal pigment epithelium (RPE). This necessitates the compartmentalization and proper substrate availability required for specialized processes such as photo-transduction. Glucose metabolism is preferential in many human cell types for adenosine triphosphate generation, yet fatty acid β-oxidation generates essential fuel for RPE. Here, we provide a brief overview of metabolic demands in both the healthy and dystrophic RPE with an emphasis on fatty acid oxidation. We outline therapies aimed at renormalizing this metabolism and explore future avenues for therapeutic intervention.

This review evaluates the current surgical management options for refractory and atypical macular holes (MH) and proposes a treatment paradigm for approaching complex cases. A review of literature was performed to deliver a thorough discussion of the epidemiology and pathophysiology of MH as well as the historic evolution of surgical management strategies. With this context established, an update on recent surgical advances for management of large, chronic, and highly myopic MH is provided. New small MH may be adequately treated with pars plana vitrectomy, while those ≥300 μm should undergo internal limiting membrane (ILM) peel. For MH ≥400 μm with risk factors for failure, primary intervention should involve creation of an ILM flap and various methods of flap creation are discussed. For very large MH ≥700 μm or in refractory cases, autologous retinal transplants and other recently proposed procedures should be considered. While typical MHs enjoy high initial surgical success rates, atypical and refractory MH require additional intraoperative and postoperative considerations to maximize surgical success and optimize vision. With many techniques at the surgeon's disposal, patient selection becomes critical to improving outcomes.

The coronavirus disease 2019 (COVID-19) has become a global pandemic since December 2019. Although COVID-19 primarily affects the respiratory systems, it has become abundantly clear that it involves multiple organs including the heart, kidney, skin, and brain. Neuro-ophthalmic signs and anterior segment inflammation of the eyes were documented in COVID-19 patients recently. Small but growing number of literatures has also reported the cases of new onset vitreoretinal disorders related to COVID-19 infection. A comprehensive search from four online databases was done. Findings show vitreoretinal involvement in COVID-19 patients including the central retinal vein occlusion, central retinal artery occlusion, reactivation of previous uveitis, chorioretinitis, macular hemorrhage, acute macular neuroretinopathy, paracentral acute middle maculopathy, vitritis with outer retinal abnormalities, varicella zoster virus-related acute retinal necrosis in immunocompromised patient, and other posterior segment pathological changes. The hypotheses for potential pathogenesis of these manifestations are direct viral ocular infection and thromboembolic complications secondary to the hyperinflammatory response. This is the first review article, which provides an overview of current evidence regarding the vitreoretinal manifestations in COVID-19 patients.

PURPOSE: To determine the patient-centered effectiveness of switching patients with persistent macular edema due to retinal vein occlusion (RVO) to aflibercept using the National Eye Institute Visual Function Questionnaire 25 (NEI-VFQ-25). MATERIALS AND METHODS: Prospective study of eyes with persistent cystoid macular edema due to RVO despite regular treatment with bevacizumab or ranibizumab switched to aflibercept. Three loading doses of intravitreal aflibercept were administered every 4 weeks and thereafter every 8 weeks until week 48. Vision-related quality of life (VRQoL) using NEI-VFQ-25 was measured at baseline, 24 weeks, and 48 weeks following the switch. Baseline scores were compared to week 24 and 48 using paired t-test. Relationship between best-corrected visual acuity (BCVA) in the study eye and the NEI-VFQ-25 composite and subscale scores was investigated. RESULTS: Eighteen patients with RVO were enrolled in the study with a mean age of 70.3 ± 8.6 years. The mean change in BCVA and central macular thickness (CMT) from baseline to 48 weeks was +20.6 ± 5.2 Early Treatment of Diabetic Retinopathy Score letters and −109.2 ± 82.8 μm, respectively. VRQoL improved significantly, with an increase of mean NEI-VFQ composite score of 11.5 ± 9.5; the corresponding improvements in near and distant activities were 13.3 ± 19.4 and 8.4 ± 10.4, respectively (P < 0.001 for both). Logistic regression analysis demonstrated that BCVA gain of >15 letters and CMT < 300 μm at the end of the study predicted a higher change in VFQ-25. CONCLUSION: Switching eyes with persistent macular edema due to RVO to aflibercept resulted in significant improvement in visual function and patient satisfaction.

PURPOSE: The purpose of this study is to compare the efficacy of intravitreal ranibizumab (IVR) alone and concurrent IVR with posterior subtenon triamcinolone acetonide (PSTA) injection for patients with diabetic macular edema (DME) refractory to IVR monotherapy. MATERIALS AND METHODS: We enrolled 43 eyes of 43 patients with DME who received at least three times of IVR, which resulted in poor anatomical responses, with central foveal thickness (CFT) reduction <10% and postinjection CFT >300 μm. All the eyes received initial 3 monthly then pro re nata (PRN) IVR 0.5-mg injections. Twenty eyes continued PRN injections and 23 eyes received combined IVR 0.5 mg and PSTA 40 mg with at least 1-year follow-up. Best-corrected visual acuity (BCVA) and CFT were recorded from 1-month to 1-year follow-up. RESULTS: Following switch to combined therapy, the mean BCVA significantly improved from 0.61 ± 0.32 logarithm of the minimum angle of resolution (logMAR) to 0.45±0.39 logMAR at 6 month (P = 0.003), 0.43±0.35 logMAR at 9 months (P < 0.001), and 0.48±0.45 logMAR at 1 year (P = 0.03). In eyes with IVR alone, no significant VA improvement was noted throughout the year. Significantly better BCVA was noted in the combined group at 6-month, 9-month, and 1-year follow-up compared to IVR-alone group. The timing of combined therapy showed a significant association with 1-year BCVA (t = 3.25, P = 0.018). CONCLUSION: Concurrent IVR and PSTA resulted in significantly better visual outcomes in 1-year follow-up for those refractory to preceding ranibizumab monotherapy for DME. Early addition of PSTA predicted a better visual outcome.

PURPOSE: The purpose is to evaluate functional changes after ocriplasmin injection to treat vitreomacular traction (VMT) by microperimetry. MATERIALS AND METHODS: Prospective interventional study on patients underwent an intravitreal ocriplasmin injection. Optical coherence tomography, best-corrected visual acuity (BCVA) test, and microperimetry were performed at baseline, 1 week, 1 and 3 months. Microperimeter recorded retinal sensitivity (RS) and central retinal sensitivity (CRS) at central 12° and 4°, respectively, and fixation as bivariate contour ellipse area (BCEA) at 68%, 95%, and 99% of fixation points. Functional parameters were analyzed in patients who had (Group A) or not (Group B) VMT release. RESULTS: Twenty-one patients including 18 with VMT and 3 with VMT plus macular hole (MH) were treated. Eleven patients achieved VMT resolution including all cases with MH that achieved hole closure. An impairment of BCVA, RS and CRS (P < 0.01; P < 0.001; P = 0.001, respectively) was reported at 1 week followed by a significant improvement (BCVA, P = 0.001; RS, CRS, P = 0.02) at 3 months. The early impairment of visual acuity and sensitivity significantly occurred in Group B (P ≤ 0.01) while their recovery significantly occurred in Group A (P < 0.01). BCEA significantly increased in dimension (68%, P = 0.01; 95%, P = 0.03) at 1 week, subsequently returning to near baseline values over follow-up. Only in Group A, fixation stability significantly improved at 3 months. CONCLUSION: Microperimetry confirms an early and reversible functional impairment after ocriplasmin injection regardless VMT resolution. If a greater decrease in function could occur in the eyes without VMT resolution, a better functional recovery could occur in the event of VMT resolution.

PURPOSE: The aim of this study is to evaluate the functional and anatomical effects of switching from bevacizumab to aflibercept in patients with persistent diabetic macular edema (DME) resistant to bevacizumab. MATERIALS AND METHODS: Patients with DME refractory to bevacizumab (1.25 mg/0.05 mL) were subsequently switched to aflibercept. The included patients received five loading doses of intravitreal aflibercept (2 mg/0.05 mL) given monthly. After the loading dose, aflibercept was injected every 2 months. The follow-up duration was 1 year. RESULTS: The study consisted of 37 eyes of 37 patients. The mean age of the participants was 56.81 ± 7.11 years. The mean central macular thickness at baseline was 428.32 ± 84.89 μm, which decreased significantly to 275.54 ± 50.24 μm (P < 0.003). There was a significant improvement in the mean best-corrected logMAR visual acuity from 0.627 ± 0.307 at baseline to 0.203 ± 0.235 (P < 0.017) at the end of follow-up. CONCLUSIONS: Aflibercept is effective in patients with persistent DME not responsive to bevacizumab.

PURPOSE: The aim of this study was to evaluate the effect of inverted internal limiting membrane (ILM) flap technique and measure the retinal sensitivity using microperimetry-1 (MP-1) test in patients with large macular hole (MH). MATERIALS AND METHODS: We enrolled patients undergoing surgery for idiopathic MHs from January 2016 to October 2019. Only patients having a minimum diameter of idiopathic MH exceeding 500 μm were included in this study. All patients underwent complete preoperative ophthalmologic examinations, optical coherence tomography (OCT), and best-corrected visual acuity (BCVA) measurements. Postoperative OCT and BCVA were evaluated at least 3 months postoperatively. In addition, these patients also received MP-1 pre- and postoperatively for retinal sensitivity measurement. RESULTS: Totally ten patients (ten eyes) were included for analysis. The mean retinal sensitivity within central 12° and 40° was statistically improved after surgery (P < 0.05). The number of absolute or relative scotoma (stimulus values ≤4 dB) within central 4° showed a significant reduction postoperatively. There was also a significant increase in visual acuity postoperatively. CONCLUSION: Patients with large MH have a great successful rate by receiving inverted ILM flap technique. In our study, all MHs of ten eyes were closed postoperatively. The results also demonstrated that ILM flap technique improves both the functional and anatomic outcomes.

PURPOSE: The aim of this study is to analyze the effects of age on intraocular lens (IOL) attributes preference. MATERIALS AND METHODS: We enrolled 4213 eyes that underwent smooth phacoemulsification and IOL implantation between January 2005 and June 2018. Patients were subdivided into six groups according to their ages, i.e.,≤40, 41–50, 51–60, 61–70, 71–80, and ≥ 81 years old. The difference in preference of IOL attributes regarding age, gender, and year of surgery was analyzed separately. The analyzed IOL attributes included asphericity, astigmatism-correction, presbyopia-correction, and blue-blocking function. RESULTS: The patients averaged 68.3 ± 11.6 years old at the time of surgery. There was no significant difference in age between males and females. There were 1980 patients (47.0%) selected aspheric IOL, 822 patients (19.5%) selected multifocal (MF) IOL, 93 patients (2.2%) selected toric IOL, and 859 patients (20.4%) selected blue-blocking IOL. Adoption of aspheric and MF IOL increased significantly during the study (P < 0.001 for both attributes). There were more young patients selected aspheric and MF IOL (P < 0.001 for both), and the change in the trend of adoption over the years was also most significant in the young group (P < 0.001 for both). The proportion of patients that selected blue-blocking IOL decreased significantly after 2011 (P < 0.001). There was no gender preference in aspheric, MF, and toric IOL selection. However, there were more male patients selected blue-blocking IOL (P = 0.018). CONCLUSION: The adoption of IOLs with emerging technologies increased significantly over the years. Younger adults tended to adopt advanced technology IOL more than the older ones.

PURPOSE: The purpose of the study was to investigate the efficacy of adjunctive low-dose mitomycin-C (MMC) during successful lacrimal duct probing in adults with nasolacrimal ducts (NLDs) stenosis. MATERIALS AND METHODS: This is a prospective case–control study on patients with NLD stenosis who were randomized into two groups. All patients underwent probing without or with an application of MMC. Former group received 0.2 mg/ml MMC irrigation for 5 min. The main outcome measures were objective evaluation of patency with irrigation, as well as patients' subjective assessment of improvement. RESULTS: There were 73 eyes in 58 consecutive patients; patient mean age ranged from 19 to 78 years (mean 44 years). Female included larger group of patients (63%) and mean duration of the symptoms was 26.1 months (range, 2–120 months). After mean follow-up of 11 months (range, 9–14 months), 23 (60%) of the 38 eyes in the MMC groups and 8 (22%) of the 35 eyes in control group had complete response and remained symptom free. This difference was statistically significant (P = 0.005). According to the patient's satisfaction, epiphora was partially improved in 6 (17%) eyes of control group and 4 (10%) eyes in MMC group. Application of MMC has a better outcome in patients with severe stenosis (P = 0.007); patients who had symptoms more than 12 months (P = 0.02) and patients with constant epiphora were compared with intermittent symptoms (P = 0.001). No complications were detected during patients follow-up. CONCLUSION: This study suggests acceptable long-term results for probing adjunctive with MMC irrigation for adults with NLD stenosis that can be recommended as a simple and effective procedure for these patients.

A 6-year-old boy was referred from the optometrist for bilateral painless blurred vision of 2 weeks duration during routine screening. Upon examination, best-corrected visual acuity was 20/200 (right eye) and 20/120 (left eye). Anterior segment examination was normal for both eyes. Funduscopy showed bilateral optic disc swelling with peripapillary exudates and diffuse retinochoroiditis involving the posterior pole. Optical coherence tomography revealed diffuse retinal thickening with intraretinal fluids and cystoid changes of central fovea. Fluorescein angiography showed bilateral hot discs with vasculitis in all quadrants and large areas of nonperfusion at peripheral retina. The patient was initially treated as presumed ocular tuberculosis (TB) based on clinical presentation and history of contact with family member having pulmonary TB. Antituberculous therapy was started and both eyes received panretinal laser photocoagulation. After 3 weeks of anti-TB treatment, serology for Bartonella turned out to be positive. Treatment was changed to intravenous ceftriaxone for 10 days followed by oral cotrimoxazole for 6 weeks and combined treatment with oral prednisolone. Gradual clinical improvement was seen with corresponding visual gain due to the reduction of macular edema, but residual thickening remained due to its chronicity.

Traumatic cyclodialysis clefts, a rare diagnosis after blunt injury to the eye, are typically amenable to closure with either medical therapy or direct surgical cyclopexy. However, when cyclodialysis clefts cannot be closed through these methods, unorthodox techniques may be required. We describe a method to close a traumatic cyclodialysis cleft involving simultaneous vitrectomy, capsular tension ring placement, and insertion of an intraocular lens.

A 25-year-old female presented with sudden onset diminution of vision in the right eye (oculus dextrus [OD]) following blunt trauma after a sports injury. Ocular examination revealed best-corrected visual acuity (BCVA) of 20/30 in OD and fundus revealed commotio retinae, localized preretinal bleed, and a large choroidal rupture (CR). She was managed conservatively at that moment. Three months following trauma, she returned with further deterioration of BCVA (20/80) in OD. Optical coherence tomography angiogram (OCTA) confirmed the presence of choroidal neovascular membrane (CNVM). She was treated with single intravitreal ranibizumab injection. Repeat OCTA after 6 weeks showed the regression of CNVM. Her BCVA improved to 20/30 at 6 months of follow-up. In the index report, we present a unique OCTA guided the diagnosis of posttraumatic CR-associated CNVM and its successful management with single intravitreal ranibizumab.

The purpose of this study is to describe a surgical technique and report the functional outcome of treating nonarteritic central retinal artery occlusion (CRAO) in 2 eyes of two consecutive male patients. Two males (A) and (B) presented 6 days and few hours, respectively, after symptom onset with the clinical features typical of CRAO, including sudden severe deterioration of vision to counting fingers and a cherry-red spot in the left and right fovea, respectively. While A had been on recent treatment for hypertension and hyperlipidemia, B had no significant medical history. Both patients underwent surgery, A, 9 days, and B, <15 h after symptom onset. Surgery involved a vitrectomy, lowering of intraocular pressure (<3 mmHg), and gradual increase of arterial pressure to 165/100 mmHg (through the slow injection of intravenous adrenaline). Intraoperatively, this resulted in immediate perfusion and visible dilation of the blood-filled central retinal artery (CRA) and retinal arteriolar network and dilatation of the central retinal vein. The final vision settled to 6/60 in A and 6/36+1 in B. Although preoperative macular infarction persisted in both eyes as demonstrated by optical coherence tomography angiography, both patients claim a convincing subjective visual benefit. The procedure appeared to have positively changed the natural history of the disease in both eyes. Vitrectomy with the manipulation of intraocular and arterial pressures significantly increases ocular perfusion along the entire CRA, which can dislodge CRA thrombo-emboli and has the potential to restore retinal perfusion and improve visual outcome if undertaken before irreversible retina damage. This is a relatively straightforward technique and should join the list of surgical techniques for treating CRAO.

Cone–rod dystrophy (CORD) is a type of progressive hereditary retinal dystrophies that causes cone predominant photoreceptor degeneration characterized by wide genotypic and phenotypic heterogeneity. Macular cyst (MC) occurs very infrequently in the pediatric age group and has rarely been described in CORD. We report a case of young-onset CORD that was affected by an isolated ABCA4 mutation complicated by the development of MC. Through serial spectral-domain ocular coherence tomography MC has been observed to persist for 24 months before its resolution, followed by retinal thinning and macular atrophy with corresponding visual acuity decline. The formation of MC and visual acuity appeared to be directly correlated in ABCA4-related CORD and its manifestation is invaluable in predicting eventual visual loss. We further speculate that dysfunctional outer blood–retinal barrier may play a role in the pathophysiology of MC development in CORD.

Ophthalmic vascular occlusion is an infrequent but devastating complication following cosmetic facial filler injection. We report a case of developing retinal artery occlusion after poly-L-lactic acid (PLLA) injection. A 49-year-old woman with multiple chronic diseases experienced sudden central visual loss and severe ocular pain in the right eye immediately after PLLA injection in the temporal region. Her best-corrected visual acuity in the right eye dropped from 20/20 to 20/200. Fundus photography showed marked optic disc edema and localized retinal whitening in the territory of the blocked vessels. Spectral-domain optical coherence tomography revealed localized hyperreflectivity of the inner retina and retinal edema. Fluorescein angiography showed delayed filling of the retinal arteries and absence of retinal perfusion in the affected areas. Despite prompt aggressive management of the condition with ocular massage, topical brimonidine eyedrops, and hyperbaric oxygen therapy, the patient suffered permanent visual loss due to optic atrophy. Among all the subcutaneous filler materials, PLLA has not been a common cause of vascular complications, especially when injected in the temporal region, as this area has not been considered dangerous in the previous literature. Practitioners should be aware of the risk of visual loss, and extra care should be given on those who originally have a higher risk for vascular complications.

We report a case of retinal pigment epithelial tear in a patient with peripheral exudative hemorrhagic chorioretinopathy (PEHCR). A 60-year-old diabetic female presented with left eye metamorphopsia. Fundus examination showed bilateral peripheral retinal pigment epithelium (RPE) degeneration, and a large serpentine-shaped RPE degeneration tract extending from the superotemporal arcade to the inferior periphery with associated subretinal hemorrhages in her left eye. This tract curved around the fovea, just sparing it. Fundus fluorescein and indocyanine green angiographies showed bilateral polyps in the superotemporal periphery. Optical coherence tomography through the tract showed scrolled up RPE at its edges with bare underlying Bruch's membrane and choroid in the region of the rip. There was no sign of an underlying pigment epithelial detachment. The patients with PEHCR should be prognosticated about such a rare vision-threatening macular complication.