Manifestations of intraocular inflammation over time in patients on brolucizumab for neovascular AMD

Purpose To describe the adverse events associated with brolucizumab, in particular the sequence of intraocular inflammation (IOI), retinal vasculitis (RV), and/or retinal vascular occlusion (RO). Methods This was an unmasked post hoc analysis of the randomized HAWK/HARRIER clinical trials. Patients with neovascular AMD in the brolucizumab arms of the trials were included. IOI-related adverse events reported by study investigators were analyzed to determine early signs and the time course of IOI-related adverse events, using a subgroup of patients with definite/probable IOI cases identified in an independent unmasked post hoc review by an external safety review committee. A limited literature review on IOI following anti-VEGF therapy was also conducted. Results Among 50 patients with definite/probable IOI cases identified by the safety review committee, 12 had RV or RO adverse events reported by the investigators. For 6 of 12, IOI (other than RV) was reported before RV or RO. The duration from the first IOI adverse event to the first RV or RO adverse event ranged from 16 to 171 days for 5 patients and was 553 days for 1 patient. Four of the 6 patients received ≥ 1 brolucizumab injection on or after the date of the first IOI adverse event and before the first RV or RO adverse event. Conclusions IOI may precede RV or RO in some patients treated with brolucizumab.

Laser treatment of macular retinal folds in late postoperative period after retinal detachment repair

Macular retinal folds are a rare yet grave complication of surgical rhegmatogenous retinal detachment repair. Clinical symptoms vary depending on the location and severity of folding. Fold located in the periphery of the ocular fundus can be asymptomatic, but macular retinal folds cause diminished visual acuity and metamorphopsia. Currently, the most effective treatment for retinal folds is repeat surgery. Its serious disadvantage is the risk of complications in the early postoperative period, including hemophthalmia, inflammation, secondary glaucoma, cataracts, RRD recurrence, macular tears, retinal vascular occlusion, etc. The clinical case described below demonstrates the potential of combination laser therapy for the treatment of macular retinal folds based on the use of modern diagnostic and therapeutic methods.

Uveitis and Rheumatological Diseases

Uveitis is the most common ophthalmological disorder in the field of rheumatology, accounting for a significant proportion of visual morbidity, both locally and internationally. Causative factors can be divided into infectious and noninfectious etiologies. The diagnosis of uveitis is a major challenge due to heterogeneity in presentation. The disease course may be acute monophasic, recurrent, or chronic relapsing. Complications include posterior synechiae, secondary cataract, ocular hypertension or glaucoma, macular edema, retinal vascular occlusion, epiretinal membrane, and so on, and ultimately visual loss. Antimicrobial therapy is indicated for infection, whereas noninfectious uveitis warrants a combination of steroids, immunosuppressives, and anti-inflammatory agents. With the advancement of biologics, treatment strategies in chronic, noninfectious uveitis have had multiple breakthroughs, particularly in treatment-resistant cases. This article provides a review of the diagnostic approach to uveitis based on symptomatology and ophthalmological findings, and discussion of relevant treatment modalities and strategies.

Retinal artery occlusion as a probable idiosyncratic reaction to topical minoxidil: a case report

Background Minoxidil hair formulation is commonly used for the treatment of male or female androgenic alopecia. This over-the-counter product is considered safe, but should be used with caution. Ocular side effects following topical minoxidil use are rarely reported. In this paper, we report a rare case of inferior hemiretinal artery occlusion possibly caused by topical 5% minoxidil treatment. Case description A 21-year-old Asian Indian male presented to the retina clinic with sudden onset blurring of vision and superior visual field loss in the right eye since morning. He was diagnosed with androgenic alopecia and was on treatment with topical 5% minoxidil spray twice a day for the last 3 years. On examination, his corrected distance visual acuity was 6/6, N6 in both eyes. Anterior segment examination and intraocular pressure in both eyes and left eye fundus were within normal limits. Right eye fundus examination showed features suggestive of inferior hemiretinal artery occlusion, which were confirmed on fluorescein angiography and optical coherence tomography. A detailed systemic evaluation and investigations (blood pressure, random blood sugar, hematological and coagulation profile, serum homocysteine level, Mantoux test, chest x-ray, cardiac two-dimensional echography, thyroid function test, and immunological profile) did not detect any abnormalities. The ocular condition and its visual prognosis were explained to the patient, and he was asked to review after 4 weeks. Conclusion Though there is no definite cause–outcome relationship between topical minoxidil use and retinal artery occlusion development, this possibility should be kept in mind when observing retinal vascular occlusion cases with concurrent use of topical minoxidil.

Association between Statins and Retinal Vascular Occlusion: A Population-Based Cohort Study

Retinal vascular occlusion (RVO), including retinal arterial occlusion and retinal vein occlusion, is a common retinal vascular disease that causes visual disturbance. The exact pathogenesis of RVO remains unclear. In all types of RVO patients, hyperlipidemia is more than twofold more common than in controls. Statins have been used to control blood cholesterol levels and have been found to reduce the risk of cardiovascular morbidity and mortality. Moreover, the immunomodulatory functions of statins may play a role in treating inflammatory diseases. This study aimed to evaluate whether patients taking statins have a lower risk of developing RVO compared to patients not taking statins. Adult patients with statins usage on the index date identified from the Taiwan National Health Insurance Research Database (NHIRD) between 2000 and 2013 were included. A threefold matched group was selected using age, sex, and year of index date for comparison. During the mean follow-up period of 12.87 ± 1.88 years, the cumulative incidence of RVO was significantly lower in the statin-user group (29.96 per 105 person-years [PYs]) than in the non-statin-user group (39.35 per 105 PYs). The results showed a lower cumulative incidence rate of RVO in patients prescribed statins than in those not prescribed statins (log-rank test, p = 0.020). The adjusting hazard ratio (HR) was significantly greater for RVO in the statin-user group (adjusted HR, 0.704; 95% CI, 0.591–0.873). Statin users had a decreased risk for all types of RVO development, including central retinal artery occlusion, arterial branch occlusion, central retinal vein occlusion, and branch retinal vein occlusion. In conclusion, patients undergoing statin treatment have a lower risk of developing RVO compared to patients not taking statins.

Baicalein, Baicalin, and Wogonin: Protective Effects against Ischemia-Induced Neurodegeneration in the Brain and Retina

Ischemia is a common pathological condition present in many neurodegenerative diseases, including ischemic stroke, retinal vascular occlusion, diabetic retinopathy, and glaucoma, threatening the sight and lives of millions of people globally. Ischemia can trigger excessive oxidative stress, inflammation, and vascular dysfunction, leading to the disruption of tissue homeostasis and, ultimately, cell death. Current therapies are very limited and have a narrow time window for effective treatment. Thus, there is an urgent need to develop more effective therapeutic options for ischemia-induced neural injuries. With emerging reports on the pharmacological properties of natural flavonoids, these compounds present potent antioxidative, anti-inflammatory, and antiapoptotic agents for the treatment of ischemic insults. Three major active flavonoids, baicalein, baicalin, and wogonin, have been extracted from Scutellaria baicalensis Georgi (S. baicalensis); all of which are reported to have low cytotoxicity. They have been demonstrated to exert promising pharmacological capabilities in preventing cell and tissue damage. This review focuses on the therapeutic potentials of these flavonoids against ischemia-induced neurotoxicity and damage in the brain and retina. The bioactivity and bioavailability of baicalein, baicalin, and wogonin are also discussed. It is with hope that the therapeutic potential of these flavonoids can be utilized and developed as natural treatments for ischemia-induced injuries of the central nervous system (CNS).

Clinical Characteristics of Paracentral Acute Middle Maculopathy in Eyes with Retinal Vascular Occlusion Diseases in Chinese Patients

Aim. To investigate the incidence and clinical characteristics of paracentral acute middle maculopathy (PAMM) and its relationship with prominent middle limiting membrane (p-MLM) sign in eyes with retinal artery occlusion (RAO) or retinal vein occlusion (RVO) in a Chinese clinical setting. Methods. In this retrospective observational study from January 2015 to May 2020, multimodal imaging data of 807 eyes including 555 consecutive patients with RVO or 252 consecutive patients with RAO were reviewed. All patients were scanned using the spectrum-domain optical coherence tomography (OCT), and some of them underwent color fundus photography, fundus fluorescence angiography, en face OCT, and OCT angiography. Results. PAMM was detected in 49 eyes of 49 RAO patients and 29 eyes of 29 RVO patients. The mean ages at presentation were 64.49 ± 13.90 years and 54.00 ± 18.48 years in RAO and RVO patients ( P = 0.006 ), respectively. Eyes with RAO were more prone to develop PAMM (19.44% [49/252] vs. 5.23% [29/555]; P < 0.001 ). Of the 78 eyes with PAMM, 24 eyes (7 eyes with RVO and 17 eyes with RAO) were found with p-MLM sign. An interesting phenomenon that had been overlooked before was that the hyperreflective line of the p-MLM sign was usually continuous, regardless of the type of PAMM lesion. Conclusions. This series is the largest to date to describe the clinical characteristics of PAMM and p-MLM sign in Chinese patients. The incidence of PAMM and p-MLM sign in patients with RAO was relatively higher than that in patients with RVO. These signs alone probably represent milder ischemia and prompt us to carry out a comprehensive and meticulous examination to prevent the further development of the disease. In addition, the hyperreflective line of the p-MLM sign was usually continuous, which could support the totally venous nature of the retinal deep capillary plexus to some extent.