Oculometric biomarkers of visuomotor deficits in clinically asymptomatic patients with systemic lupus erythematosus undergoing long-term hydroxychloroquine treatment.

Introduction: This study examines a set of oculomotor measurements, or "oculometric" biomarkers, as potential early indicators of visual and visuomotor deficits due to retinal toxicity in asymptomatic Systemic Lupus Erythematosus (SLE) patients on long-term hydroxychloroquine (HCQ) treatment. The aim is to identify subclinical functional impairments that are otherwise undetectable by standard clinical tests and to link them to structural retinal changes. Methods: We measured oculomotor responses in a cohort of SLE patients on chronic HCQ therapy using a previously established behavioral task and analysis technique. We also examined the relationship between oculometrics, OCT measures of retinal thickness, and standard clinical perimetry measures of visual function in our patient group using Bivariate Pearson Correlation and a Linear Mixed-Effects Model (LMM). Results: Significant visual and visuomotor deficits were found in 12 asymptomatic SLE patients on long-term HCQ therapy compared to a cohort of 17 age-matched healthy controls. Notably, six oculometrics were significantly different. The median initial pursuit acceleration was 22%, steady-state pursuit gain 16%, proportion smooth 7%, and target speed responsiveness 31% lower, while catch-up saccade amplitude was 46% and fixation error 46% larger. Excluding the two patients with diagnosed mild toxicity, four oculometrics, all but fixation error and proportion smooth, remained significantly impaired compared to controls. Across our population of 12 patients (24 retinae), we found that pursuit latency, initial acceleration, steady-state gain, and fixation error were linearly related to retinal thickness even when age was accounted for, while standard measures of clinical function (Mean Deviation and Pattern Standard Deviation) were not. Discussion: Our data show that specific oculometrics are sensitive early biomarkers of functional deficits in SLE patients on HCQ that could be harnessed to assist in the early detection of HCQ-induced retinal toxicity and other visual pathologies, potentially providing early diagnostic value beyond standard visual field and OCT evaluations.

Electroretinographic findings in retinal vasculitis.

AIM: To describe and correlate electroretinographic responses with clinical and angiographic findings in retinal vasculitis (RV). METHODS: Medical records of patients with diagnosis of RV at a tertiary eye centre from December 2017 to May 2021 were reviewed. Cases in which fluorescein angiography (FFA) and full field electroretinography (ffERG) were done within 1 month were included. FFAs were graded according to the Angiography Scoring for Uveitis Working Group from 0 to 40, where 0 is normal. A novel ffERG grading system was implemented where individual waves were graded for timing and amplitude and general ffERG score was determined with 6 being a perfect score. RESULTS: 20 patients (34 eyes) were included. Mean age was 43.9±19.8 years; 70% were female. Median best-corrected visual acuity was 0.8 (0.08-1). Mean FFA score was 12.6±6.5. Median general ffERG score was 5 (0-6). 68% and 91% of eyes had responses with general ffERG scores ≥5 and 4, respectively. Flicker timing was most commonly affected.FFA scores weakly correlated with delayed photopic cone b-wave and flicker timing (p=0.03 and 0.016, respectively). Vitreous haze moderately correlated with delayed cone b-wave timing (p<0.001), delayed flicker timing (p=0.002) and weakly correlated with lower flicker amplitude (p=0.03). Underlying systemic disease was associated with poor ffERG responses. CONCLUSION: In this study, RV was not frequently associated with severe global retinal dysfunction Higher FFA scores, and vitreous haze grading were weakly, but significantly, correlated with cone-generated ffERG responses.

Photodynamic Therapy-Induced Macular Hole.

A 72-year-old female with neovascular macular degeneration refractory to anti-vascular endothelial growth factor injections underwent photodynamic therapy and subsequently developed a macular hole (MH) associated with vitreomacular traction. After a period of observation, the MH enlarged. Pars plana vitrectomy was performed, and the MH was closed successfully. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:270-272.].

Rapid Onset of Retinal Toxicity From High-Dose Hydroxychloroquine Given for Cancer Therapy.

PURPOSE: To report rapid onset of retinal toxicity in a series of patients followed on high-dose (1000 mg daily) hydroxychloroquine during an oncologic clinical trial studying hydroxychloroquine with erlotinib for non-small cell lung cancer. DESIGN: Retrospective observational case series. METHODS: Ophthalmic surveillance was performed on patients in a multicenter clinical trial testing high-dose (1000 mg daily) hydroxychloroquine for advanced non-small cell lung cancer. The US Food & Drug Administration-recommended screening protocol included only visual acuity testing, dilated fundus examination, Amsler grid testing, and color vision testing. In patients seen at Stanford, additional sensitive screening procedures were added at the discretion of the retinal physician: high-resolution spectral-domain optical coherence tomography (OCT), fundus autofluorescence (FAF) imaging, Humphrey visual field (HVF) testing, and multifocal electroretinography (mfERG). RESULTS: Out of the 7 patients having exposure of at least 6 months, 2 developed retinal toxicity (at 11 and 17 months of exposure). Damage was identified by OCT imaging, mfERG testing, and, in 1 case, visual field testing. Fundus autofluorescence imaging remained normal. Neither patient had symptomatic visual acuity loss. CONCLUSIONS: These cases show that high doses of hydroxychloroquine can initiate the development of retinal toxicity within 1-2 years. Although synergy with erlotinib is theoretically possible, there are no prior reports of erlotinib-associated retinal toxicity despite over a decade of use in oncology. These results also suggest that sensitive retinal screening tests should be added to ongoing and future clinical trials involving high-dose hydroxychloroquine to improve safety monitoring and preservation of vision.

Macular infarction following intravitreal bevacizumab for treatment of central retinal vein occlusion.

Bevacizumab, a monoclonal antibody against vascular endothelial growth factor (VEGF), is widely used for the treatment of macular edema associated with central retinal vein occlusion (CRVO). The authors present a series of three patients with CRVO who suffered apparent macular infarction within weeks of intravitreal administration of bevacizumab. Of the nearly 200 patients undergoing intravitreal injections of bevacizumab for this indication over a surveillance period of 3 years, this event occurred in three patients. This has not been described in the natural history of the disease and is associated with poor visual outcomes.

Therapeutic window of retinal photocoagulation with green (532-nm) and yellow (577-nm) lasers.

BACKGROUND AND OBJECTIVE: The 577-nm (yellow) laser provides an alternative to the 532-nm (green) laser in retinal photocoagulation, with potential benefits in macular treatment and through ocular opacities. To assess relative risk of thermomechanical rupture of Bruch's membrane with yellow laser in photocoagulation, the therapeutic window, the ratio of threshold powers for mild coagulation and rupture, was measured. MATERIALS AND METHODS: Retinal coagulation and rupture thresholds, visualized ophthalmoscopically, were measured with 577- and 532-nm lasers using 10- to 100-ms pulses in 34 rabbit eyes. Lesions at 1 and 7 days were assessed histologically. RESULTS: Coagulation threshold with yellow laser was 26% lower than with green laser. The therapeutic window increased linearly with log-duration for both wavelengths with a difference in parallel-slope intercept of 0.36 ± 0.20, corresponding to 8% to 15% wider therapeutic window for yellow wavelength. CONCLUSION: The therapeutic window of retinal photocoagulation in rabbits at 577 nm is slightly wider than at 532 nm, whereas histologically the lesions are similar.