Temporal macular thinning: a salient sign of Alport syndrome

Alport syndrome is a hereditary, multisystemic disorder that causes abnormalities of the ear, kidney, and eye. A teenager who was suffering from end-stage renal failure and hearing problems was referred to us suspected of Alport syndrome. He did not have any ocular complaints and wore glasses for myopic astigmatism. His best-corrected visual acuity was 6/7.5 bilaterally. Anterior segment examination was unremarkable. Posterior segment examination showed perimacular dot-andfleck retinopathy with bull’s eye maculopathy. Optical coherence tomography revealed temporal macular thinning. The findings were in keeping with the diagnosis of X-linked Alport syndrome. Ocular findings can help diagnose Alport syndrome. Early detection and treatment can help delay the progression of kidney failure.

POS1393 QUANTITATIVE AUTOFLUORESCENCE FINDINGS IN PATIENTS UNDERGOING HYDROXYCHLOROQUINE TREATMENT

Background:Hydroxychloroquine (HCQ) is a relatively safe and effective drug widely used as primary or adjunctive treatment for several rheumatological and dermatological disorders1. HCQ modulates immune response through several mechanisms and has a tropism for pigmented ocular tissues, particularly retinal pigment epithelium (RPE)2. Its accumulation within RPE cells can lead to sight threatening retinal toxicity, with bull’s eye maculopathy (BEM) representing its advanced phenotype. 3 Quantitative Auto-Fluorescence (qAF) is an imaging modality that allows the measurement of retinal auto-fluorescence following short-wavelength light (488nm) excitation of retinal fluorophores (lipofuscin). 4 Two recent studies have focused on qAF values in patients treated with HCQ 5,6. In both cases qAF was increased in eyes with BEM. Furthermore, Reichel et al.6 were able to detect increased values of qAF in patients without BEM as early as 6 months after the start of HCQ treatment using an experimental imaging analysis procedure.Objectives:To measure quantitative autofluorescence (qAF) in patients under treatment with hydroxychloroquine (HCQ) with no apparent signs of retinal toxicity and to compare it with that of untreated subjects.Methods:Consecutive patients at risk for the development of HCQ retinal toxicity (duration of treatment >5 years or daily HCQ dose >5 mg/kg of actual body weight (ABW) and/or renal insufficiency)7 but no alterations on Spectral Domain - Optical Coherence Tomography, Short-Wavelength Autofluorescence and 10-2 Visual Field examination were recruited. Healthy subject matched by age and sex were also enrolled in the study. All subjects underwent qAF measurements in one eye. Images were analyzed using the conventional qAF grid by Delori calculating the qAF of 8 sectors of the intermediate ring and the mean of those values (qAF8).Results:Thirty-nine patients treated with HCQ (38 females, mean age 52,1 ± 8,6 years) and 39 untreated subjects (38 females, mean age 51,2 ± 8,6 years). In both HCQ patients and untreated subjects, qAF8 was positively correlated with age (p=0.004) (Figure 1). Although HCQ patients showed a higher mean qAF8 compared to untreated subjects (294,7 ±65,3 vs 268,9 ± 57,5), the difference was not significant (p=0.068). HCQ patients showed significantly higher mean qAF values in the inferior-temporal, inferior and inferior-nasal sectors of the intermediate ring of qAF grid compared to untreated subjects (all p<0.05).Figure 1.Visual representation of a model predicting the standardized qAF values as influenced by age and HCQ daily dose/ABW, calculated for a treatment duration of 15 years.Conclusion:These results suggest a possible preclinical increase of qAF values in inferior parafoveal sectors probably induced by HCQ exposure. Further studies are required to improve our understanding of preclinical stages of HCQ retinopathy and the possible role of qAF in the HCQ toxicity screening.References:[1]Haładyj, E., Sikora, M., Felis-Giemza, A. & Olesińska, M. Antimalarials - are they effective and safe in rheumatic diseases? Reumatologia56, 164–173 (2018).[2]Rosenthal, A. R., Kolb, H., Bergsma, D., Huxsoll, D. & Hopkins, J. L. Chloroquine retinopathy in the rhesus monkey. Invest. Ophthalmol. Vis. Sci.17, 1158–1175 (1978).[3]Modi, Y. S. & Singh, R. P. Bull’s-Eye Maculopathy Associated with Hydroxychloroquine. N. Engl. J. Med.380, 1656 (2019).[4]Sparrow, J. R., Duncker, T., Schuerch, K., Paavo, M. & de Carvalho, J. R. L. J. Lessons learned from quantitative fundus autofluorescence. Prog. Retin. Eye Res.74, 100774 (2020).[5]Greenstein, V. C. et al. Quantitative Fundus Autofluorescence in HCQ Retinopathy. Invest. Ophthalmol. Vis. Sci.61, 41 (2020).[6]Reichel, C. et al. Quantitative Fundus Autofluorescence in Systemic Chloroquine/Hydroxychloroquine Therapy. Transl. Vis. Sci. Technol.9, 42 (2020).[7]Yusuf, I. H., Sharma, S., Luqmani, R. & Downes, S. M. Hydroxychloroquine retinopathy. Eye (Lond).31, 828–845 (2017).Disclosure of Interests:Salvatore Parrulli: None declared, Mariano Cozzi Grant/research support from: Bayer, Nidek, Zeiss, Matteo Airaldi: None declared, Francesco Romano: None declared, Francesco Viola: None declared, Piercarlo Sarzi-Puttini: None declared, Giovanni Staurenghi Grant/research support from: Heidelberg Engineering (C), QuantelMedical (C), Centervue (C), Carl Zeiss Meditec (C), Alcon (C), Allergan (C), Bayer (C), Boheringer (C), Genentech (C), GSK (C),Novartis (C), and Roche (C), Optos (F), Optovue (F) and Centervue (F), Alessandro Invernizzi Grant/research support from: Novartis (C), Bayer (C)

Wavelength of light and photophobia in inherited retinal dystrophy

Inherited retinal dystrophy (IRD) patients often experience photophobia. However, its mechanism has not been elucidated. This study aimed to investigate the main wavelength of light causing photophobia in IRD and difference among patients with different phenotypes. Forty-seven retinitis pigmentosa (RP) and 22 cone-rod dystrophy (CRD) patients were prospectively recruited. We designed two tinted glasses: short wavelength filtering (SWF) glasses and middle wavelength filtering (MWF) glasses. We classified photophobia into three types: (A) white out, (B) bright glare, and (C) ocular pain. Patients were asked to assign scores between one (not at all) and five (totally applicable) for each symptom with and without glasses. In patients with RP, photophobia was better relieved with SWF glasses {“white out” (p < 0.01) and “ocular pain” (p = 0.013)}. In CRD patients, there was no significant difference in the improvement wearing two glasses (p = 0.247–1.0). All RP patients who preferred MWF glasses had Bull’s eye maculopathy. Meanwhile, only 15% of patients who preferred SWF glasses had the finding (p < 0.001). Photophobia is primarily caused by short wavelength light in many patients with IRD. However, the wavelength responsible for photophobia vary depending on the disease and probably vary according to the pathological condition.

Possible Retinal Impairment Secondary to Ritonavir Use in SARS-CoV-2 Patients: A Narrative Systematic Review

Some reports described a possible ritonavir-related retinal toxicity. The objective of this research was to review and analyze previous studies conducted on ritonavir administration and retinal impairment in a narrative synthesis. PubMed was used to perform a systematic review of ritonavir effects and retinal damage. All studies up to December 2019 were considered. Seven single cases and one case series, reporting a total of 10 patients affected by retinal changes secondary to long-term ritonavir treatment, were included in the review. Variable degrees of outer retina and retinal pigment epithelium changes were detected in most of the patients, with two patients showing macular telangiectasia, four patients presenting intraretinal crystal deposits, two patients disclosing a bull’s eye maculopathy, and two patients revealing midperipheral bone spicule-like pigment changes. In the present study, we hypothesized that the use of ritonavir in life-saving treatments of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) pneumonia might expose these patients to the risk of developing a retinotoxicity. We aimed to alert ophthalmologists on the importance of recognizing ritonavir-induced retinal impairment in SARS-CoV-2 patients. These findings are the target for personalized medicine.

Methoxsalen-induced advanced bull’s eye maculopathy

A number of systemic medications are known to cause macular toxicity, and bull’s eye maculopathy is caused by some of them like hydroxychloroquine and clofazimine. A 55-year-old female, known case of vitiligo with history of undergoing methoxsalen–ultraviolet A therapy, presented with painless defective vision in both eyes. Fundus examination and autofluorescence showed macular degeneration with bull’s eye configuration. Optical coherence tomography showed perifoveal loss of photoreceptors and outer retinal thinning with foveal sparing appearing as ‘flying saucer’. Multifocal electroretinogram showed pan-macular suppression of waveforms. Patient was diagnosed as case of methoxsalen-induced advanced macular toxicity. This is the first reported case of methoxsalen-induced advanced bull’s eye maculopathy.