Hydroxychloroquine Causes Early Inner Retinal Toxicity and Affects Autophagosome-Lysosomal Pathway and Sphingolipid Metabolism in the Retina.

Hydroxychloroquine (HCQ) is an anti-malarial drug but also widely used to treat autoimmune diseases like arthritis and lupus. Although there have been multiple reports of the adverse effect of prolonged HCQ usage on the outer retina, leading to bull's-eye maculopathy, the effect of HCQ toxicity on the inner retina as well as on overall visual functions has not been explored in detail. Furthermore, lack of an established animal model of HCQ toxicity hinders our understanding of the underlying molecular mechanisms. Here, using a small clinical study, we confirmed the effect of HCQ toxicity on the inner retina, in particular the reduction in central inner retinal thickness, and established a mouse model of chronic HCQ toxicity that recapitulates the effects observed in human retina. Using the mouse model, we demonstrated that chronic HCQ toxicity results in loss of inner retinal neurons and retinal ganglion cells (RGC) and compromises visual functions. We further established that HCQ treatment prevents autophagosome-lysosome fusion and alters the sphingolipid homeostasis in mouse retina. Our results affirm the notion that HCQ treatment causes early damage to the inner retina and affects visual functions before leading to characteristic toxicity in the macular region of the outer retina, 'bull's-eye maculopathy.' We also provide insights into the underlying molecular mechanisms of HCQ retinal toxicity that may involve autophagy-lysosomal defects and alterations in sphingolipid metabolism.

Social media collaboration of retinal physicians: A 'Young Retina Forum' survey.

BACKGROUND AND OBJECTIVE: To describe the impact that social media usage has on a group of retina specialists. MATERIALS AND METHODS: An anonymous online survey was sent to members of the Young Retina Forum who use the social media platform - Telegram. RESULTS: Of a total of 178 members, 100 responded (87 men and 13 women), having an average age of 35 years. Of these, 66 respondents were surgical retina attendings in practice for 3 years. In all, 98 respondents found the Young Retina Forum useful for networking and educationally valuable discussions, and 35 respondents had at least one instance when they had used Young Retina Forum to obtain assistance at that moment in the clinic and/or the operating room. At least 58 respondents said Young Retina Forum changed their practice patterns in the clinic and/or operating room. CONCLUSION: In this study, 58% of Young Retina Forum respondents said their practice patterns have changed due to their experiences using social media. Professional use of social media by ophthalmologists has the potential to improve education, clinical practice, and patient care.

Assessment of Neurotrophins and Inflammatory Mediators in Vitreous of Patients With Diabetic Retinopathy.

Purpose: To assess vitreous levels of inflammatory cytokines and neurotrophins (NTs) in diabetic retinopathy (DR) and elucidate their potential roles. Methods: A prospective study was performed on 50 vitreous samples obtained from patients with DR (n = 22) and the nondiabetic controls (n = 28). All patients were candidates for vitrectomy. Inflammatory cytokine and NT levels were determined with ELISA. Potential source and role of NTs was determined by using human retinal Müller glia and mouse photoreceptor cells and challenging them with TNF-α or IL-1ß, followed by detection of NTs and cell death. Results: Vitreous NT levels of all DR patients were significantly higher than those of nondiabetic controls (nerve growth factor [NGF, P = 0.0001], brain-derived neurotrophic factor [BDNF, P = 0.009], neurotrophin-3 [NT-3, P < 0.0001], neurotrophin-4 [NT-4, P = 0.0001], ciliary neurotrophic factor [CNTF, P = 0.0001], and glial cell-derived neurotrophic factor [GDNF, P = 0.008]). Similarly, the levels of inflammatory mediators IL-1ß (P < 0.0001), IL-6 (P = 0.0005), IL-8 (P < 0.0001), and TNF-α (P < 0.0001) were also higher in eyes with DR. Interestingly, inflammatory cytokine and NT levels, particularly TNF-α (P < 0.05), IL-8 (P < 0.004), NT-3 (P = 0.012), NGF (P = 0.04), GDNF (P = 0.005), and CNTF (P = 0.002), were higher in eyes with nonproliferative diabetic retinopathy (NPDR) than in eyes with active proliferative diabetic retinopathy (PDR). Cytokine stimulation of Müller glia resulted in production of NTs, and GDNF treatment reduced photoreceptor cell death in response to inflammation and oxidative stress. Conclusions: Together, our study demonstrated that patients with DR have higher levels of both inflammatory cytokines and NTs in their vitreous. Müller glia could be the potential source of NTs under inflammatory conditions to exert neuroprotection.

Vision Loss after Intravitreal Injection of Autologous "Stem Cells" for AMD.

Adipose tissue-derived "stem cells" have been increasingly used by "stem-cell clinics" in the United States and elsewhere to treat a variety of disorders. We evaluated three patients in whom severe bilateral visual loss developed after they received intravitreal injections of autologous adipose tissue-derived "stem cells" at one such clinic in the United States. In these three patients, the last documented visual acuity on the Snellen eye chart before the injection ranged from 20/30 to 20/200. The patients' severe visual loss after the injection was associated with ocular hypertension, hemorrhagic retinopathy, vitreous hemorrhage, combined traction and rhegmatogenous retinal detachment, or lens dislocation. After 1 year, the patients' visual acuity ranged from 20/200 to no light perception.

Endophthalmitis After Intravitreal Injections in Patients With Self-reported Iodine Allergy.

PURPOSE: To present cases of endophthalmitis following intravitreal injections where povidone-iodine (PI) was not used as part of the surgical preparation. DESIGN: Retrospective case series. METHODS: All cases of presumed injection-related endophthalmitis presenting to the Massachusetts Eye and Ear Infirmary between June 2008 and November 2014 and Dean McGee Eye Institute between January 2010 and January 2015 were identified. Patients who did not receive PI preparation owing to documented self-reported allergy to iodine, iodine-containing contrast material, or shellfish were identified and their injection histories and clinical courses reviewed. RESULTS: The combined rate of postinjection endophthalmitis at these 2 centers was 0.019%. Among 42 patients with postinjection endophthalmitis, 5 (11.9%) did not receive PI prophylaxis. The mean number of intravitreal injections without PI before the development of endophthalmitis was 10.6 with a 9.4% rate of endophthalmitis (5 cases per 53 injections). All patients underwent tap-and-inject procedures with vancomycin 1 mg and ceftazidime 2 mg. Two patients did not receive PI at the time of tap and inject; 1 of these patients required subsequent pars plana vitrectomy for worsening clinical course. Cultures were positive in 4 of 5 cases; all positive cultures grew coagulase-negative Staphylococcus. All patients who received subsequent intravitreal injections received PI prophylaxis without allergic reactions, thus demonstrating a lack of true PI allergy. CONCLUSIONS: Avoiding PI owing to self-reported iodine "allergy" risks substantial ocular morbidity. Allergy testing can be pursued per patient request or in rare cases of suspected true PI allergy; however, in cases where delayed treatment would adversely affect visual outcome, the clinician should feel confident that minimal allergic risk exists.

Hydroxychloroquine retinopathy: A review of imaging.

Hydroxychloroquine (HCQ) retinopathy can result in permanent vision loss. In early stages of HCQ retinopathy, patients are usually asymptomatic with preservation of visual acuity. We aspire that our review, in conjunction with the American Academy of Ophthalmology screening guidelines, shall shed light on effective screening measures utilizing multimodal imaging techniques to detect early signs of HCQ retinopathy before advanced changes manifest clinically.

Macular Development in Aggressive Posterior Retinopathy of Prematurity.

Purpose. To report anatomic outcomes after early and confluent laser photocoagulation of the entire avascular retina, including areas in close proximity to the fovea, in patients with APROP. We aspire to demonstrate fundoscopic evidence of transverse growth and macular development following laser treatment in APROP. Methods. Retrospective review of 6 eyes with APROP that underwent confluent laser photocoagulation of the entire avascular retina. Photographic fundoscopic imaging was performed using the RetCam to compare outcomes after treatment. Results. Mean birth weight and gestational age were 704.8 g and 24.33 weeks, respectively. There were 2 females and 1 male. The average time to laser was 9.3 weeks after birth, with the mean postmenstrual age of 34 weeks. Two eyes had zone 1 and 4 eyes had posterior zone 2 disease. Three eyes developed 4A detachments, which were successfully treated. All 6 eyes experienced transverse growth, with expansion of the posterior pole and anterior displacement of the laser treatment. Conclusion. Confluent photocoagulation of the entire avascular retina, regardless of foveal proximity, should be the mainstay for treating APROP. Examination should be conducted within 5-10 days to examine areas previously hidden by neovascularization to ensure prudent therapy. Macular development involves both transverse and anterior-posterior growth.

Conjunctival limbal autograft and allograft transplantation using fibrin glue.

BACKGROUND AND OBJECTIVE: Conjunctival limbal autograft is the surgical treatment of choice for visually significant unilateral limbal stem cell deficiency. The use of fibrin glue, which has been reported extensively in pterygium and other conjunctival surgeries, has not been fully described in limbal stem cell transplantation. PATIENTS AND METHODS: The authors reviewed 3 cases of conjunctival limbal autograft and 1 of living related conjunctival limbal allograft using only fibrin glue to secure the graft. Main outcome measures included ocular surface stability, visual acuity, and postoperative complications. RESULTS: At most recent follow-up, all 4 patients (100%) maintained a stable ocular surface. Mean epithelial healing time was 10 days. Mean visual acuity improved from 20/400 to 20/53. All grafts were successful with no postoperative dislocations or displacements. CONCLUSION: The findings demonstrate that fibrin glue can be used safely and effectively to secure conjunctival limbal grafts in limbal stem cell deficiency. This novel approach has the potential to decrease operative time, increase ease of technique, and improve patient comfort postoperatively.

Limbal allograft transplantation using fibrin glue.

Limbal transplantation is now widely accepted as the treatment of advanced limbal stem cell deficiency. Herein, we describe a technique for harvesting thin limbal grafts from cadaveric corneoscleral rims and a sutureless method to secure the grafts to the recipient eye using fibrin glue. We report the results of fibrin glue-assisted keratolimbal allograft in 19 eyes of 16 patients, with the outcome measures being ocular surface stability, visual acuity, and postoperative complications. The results indicate that limbal allograft transplantation can be performed safely and successfully using only fibrin glue to secure the grafts. This can potentially improve surgical efficiency and patient comfort postoperatively.

Screening for obstructive sleep apnea/hypopnea syndrome: subjective and objective factors.

OBJECTIVES: To determine the sensitivity and specificity of the Berlin Questionnaire and the Obstructive Sleep Apnea/Hypopnea Syndrome (OSAHS) score for individually predicting a diagnosis of OSAHS, and to propose a method for OSAHS screening incorporating objective and subjective factors. STUDY DESIGN: Cross-sectional survey. SETTING: Tertiary care center. METHODS: Charts were reviewed from 223 consecutive patients for whom complete data regarding the Berlin questionnaire, OSAHS score (Friedman tongue position + tonsil size + body mass index grade), Epworth Sleepiness Scale, and visual analog scale for snoring were obtained prior to polysomnography (PSG). Sensitivity and specificity were determined for the Berlin questionnaire and OSAHS score for predicting an apnea hypopnea index (AHI) >or= 5. Patient data were subjected to multivariate stepwise discriminant analysis and used to construct a screening system based on the Fisher's linear classification equation. Results were cross-validated by PSG findings. RESULTS: In predicting an AHI >or= 5, the sensitivity and specificity, respectively, were 0.615 and 0.226 for the Berlin questionnaire, 0.863 and 0.468 for OSAHS score, and 0.82 and 0.834 for our predictive equation. When applied case-wise to the study population, this equation correctly predicted 82.5 percent of diagnoses. Accuracy was highest for severe OSAHS (87.4%) and lowest for mild disease (77.0%). Sensitivity was lowest for mild OSAHS (0.50). CONCLUSIONS: Neither the Berlin questionnaire nor the OSAHS score alone was both highly sensitive and specific for diagnosing OSAHS. By incorporating subjective and objective metrics into a single predictive equation, sensitivity and specificity were maximized, and 82.5 percent of diagnoses were accurately predicted.

A student-initiated and student-facilitated international health elective for preclinical medical students.

INTRODUCTION: Global health education is becoming more important for developing well-rounded physicians and may encourage students toward a career in primary care. Many medical schools, however, lack adequate and structured opportunities for students beginning the curriculum. METHODS: Second-year medical students initiated, designed, and facilitated a pass-fail international health elective, providing a curricular framework for preclinical medical students wishing to gain exposure to the clinical and cultural practices of a developing country. RESULTS: All course participants (N=30) completed a post-travel questionnaire within one week of sharing their experiences. Screening reflection essays for common themes that fulfill university core competencies yielded specific global health learning outcomes, including analysis of health care determinants. CONCLUSION: Medical students successfully implemented a sustainable global health curriculum for preclinical student peers. Financial constraints, language, and organizational burdens limit student participation. In future, long-term studies should analyze career impact and benefits to the host country.