Occult retinopathy following treatment of Hepatitis C with glecaprevir/pibrentasvir (Mavyret).

BACKGROUND/PURPOSE: Medication-induced ocular toxicity is an important consideration in the differential diagnosis of unexplained visual disturbance. We present a case of visual disturbance after starting treatment with glecaprevir/pibrentasvir (Mavyret), a therapy for Hepatitis C virus approved by the FDA in 2017. METHODS: A 50-year-old male with no significant ocular history experienced bilateral visual disturbance, including visual field and acuity loss, shortly after initiating treatment with Mavyret for Hepatitis C. Examination of the anterior and posterior segments was unremarkable, and no abnormalities could be identified on multimodal imaging of the eye and brain, including MRI, SD-OCT, and fundus autofluorescence. Extensive testing for inflammatory, infectious, nutritional, and genetic etiologies for optic neuropathy and retinopathy was negative. RESULTS: Electrophysiology testing was pursued to narrow the broad differential diagnosis. Full-field electroretinography and multi-focal electroretinography detected deficiencies in the rod and cone visual pathways and attenuated electrophysiologic responses in the fovea. Pattern electroretinography and visually-evoked potentials demonstrated macula dysfunction. Taken together, electrophysiologic data suggested diffuse retinal dysfunction, which was most pronounced in the macula. CONCLUSIONS: Given the temporal relationship between Mavyret administration and vision loss in our patient, and the absence of an underlying cause after extensive evaluation, we propose that Mavyret may be associated with a toxic occult retinopathy characterized by panretinal dysfunction without clinically apparent structural findings.

Didanosine-induced Retinopathy: New Insights with Long-term Follow-up.

INTRODUCTION: Didanosine is an adenosine analog, part of the nucleoside reverse-transcriptase inhibitor family. Since the description of didanosine-induced retinopathy in the early 1990s, little is known about the progression of this toxic retinopathy and the putative underlying mitochondrial defect. OBJECTIVES: We report long-term follow-up for cases of didanosine-induced retinopathy and discuss a new hypothesis for pathophysiology based on the alteration of endogenous adenosine on the photoreceptor outer segment turnover and phagocytosis by the retinal pigment epithelium. METHODS: Ophthalmic data from six cases (12 eyes) of didanosine-induced retinopathy from a single institution were retrospectively analyzed. RESULTS: All patients displayed bilateral retinal alterations in the mid-periphery. Despite didanosine discontinuation, patients with advanced areas of patchy chorioretinal atrophy appeared to have a faster progression than those with limited lesions. Full-field electroretinogram revealed generalized rod-cone dysfunction in most cases that remained stable over time. CONCLUSION: We propose new guidelines including early screening and long-term observations.

Update on Retinal Drug Toxicities.

PURPOSE OF REVIEW: This review aims to provide an update on the clinical presentations and diagnostic findings of drug-induced retinal toxicities. RECENT FINDINGS: Several newly FDA-approved medications have been associated with acute retinal toxicities, including brolucizumab, MEK inhibitors, ulixertinib, and FGFR inhibitors. Additionally, as previously believed-to-be well-tolerated medications, such as pentosan sulfate sodium, anti-retroviral therapies, and certain intraoperative ocular medications, are used more frequently or for longer periods of time, associated toxic retinopathies and inflammatory reactions have been reported. Finally, advances in ocular imaging have revealed novel findings in hydroxychloroquine and tamoxifen maculopathies. SUMMARY: Discovery of new medications, increased frequency of use, and longer-term use have led to increased reports of retinal toxicities. Advances in retinal imaging have allowed for earlier detection of subclinical changes associated with these medications, which may help prevent progression of disease. However, more research is needed to determine the point at which vision loss becomes irreversible. Risks and benefits must be assessed prior to discontinuation of the offending, but potentially lifesaving, therapy.

AOSLO imaging in poppers maculopathy shows high resolution loss of central macular cones.

PURPOSE: To use new adaptive optics scanning laser ophthalmoscopy (AOSLO) technology to better image macular pathology in poppers maculopathy. OBSERVATIONS: A 40-year-old patient was found to have poppers maculopathy. Best corrected visual acuity was decreased to 20/40 OD and 20/50 OS, spectral domain optical coherence tomography found outer retinal disruption of the fovea, and AOSLO imaging showed significant decrease in cone density of the fovea of both eyes. CONCLUSIONS AND IMPORTANCE: Poppers maculopathy is a rare, but visually significant, complication of popper abuse. AOSLO technology demonstrates significant cone damage in poppers maculopathy. The striking loss of cones revealed by AOSLO imaging shows how AOSLO imaging can elucidate macular pathology.

Bilateral retinal toxicity as a result of poisoning with pure iodine.

Iodine is an essential mineral that is necessary for the synthesis of thyroid hormones, which can cause many diseases in the body. The application of adding potassium iodate to table salts started in Turkey in 1998. High doses of iodate cause retinal toxicity, leading to significant vision loss. A 42-year-old paranoid schizophrenic patient who attempted suicide with pure iodine was admitted with bilateral vision loss. Widespread retinal pigment epithelium (RPE), ellipsoid zone (EZ) and interdigitation zone (IZ) damage were present in the optical coherence tomography (OCT) assessment. Fundus autofluorescence (FAF) findings, which included hypoautofluorescence areas that supported this condition, were also found. In conclusion, iodate in high doses is toxic on RPE, EZ and IZ. This situation could be irreversible depending on the dose.

Multimodal imaging in iodate-induced toxic retinopathy.

INTRODUCTION: Iodine deficiency is a leading cause of preventable physical and mental retardation. Potassium iodate is used for iodine supplementation to prevent iodine deficiency. We herein report a case of toxic retinopathy following intentional ingestion of potassium iodine. CASE PRESENTATION: A 41-year-old male presented with a 5-day history of blurred vision in both eyes. His visual acuity (VA) was hand motion and his pupillary reactions were sluggish bilaterally. The fundus examination revealed bilaterally diffuse retinal pigment epithelium atrophy and secondary pigmentary changes at the posterior pole, but his peripheral fundus was relatively spared. Choroidal thinning, punctate hyperreflective dots along the retinal pigment epithelium layer, and outer retinal atrophy were the optical coherence tomography findings, which were consistent with widespread areas of retinal pigment epithelium window defects observed on fundus fluorescein angiography. The visual evoked potential test showed no response in the right eye and revealed a delay in the latency and a decrease in the amplitude of the P100 wave in the left eye. Wave b responses of the photoreceptors could not be observed in the patient's electroretinogram. After a vitamin supplementation protocol consistent with the literature, at the 4-month follow-up visit his visual acuity had improved to 0.3 in the right eye and counting fingers in the left eye. CONCLUSION: Potassium iodate toxicity is a cause of serious retinal and choroidal damage and results in severe vision loss. Hydration, hemodialysis, and antioxidants can be helpful to minimize the complications.

Retinal Diseases that Can Masquerade as Neurological Causes of Vision Loss.

PURPOSE OF REVIEW: This review aims to discuss retinal diseases that may masquerade as neurological causes of vision loss and highlights modern ophthalmic ancillary testing that can help to establish these diagnoses. RECENT FINDINGS: Retinal diseases with signs and symptoms overlapping with neurological causes of vision loss include central serous chorioretinopathy, retinal ischemia, acute macular neuroretinopathy, Acute zonal occult outer retinopathy (AZOOR) complex diseases, paraneoplastic retinopathy, retinal dystrophy, and toxic retinopathy. Diagnosis is facilitated by electrophysiologic studies and multimodal ophthalmic imaging including optical coherence tomography and fundus autofluorescence imaging. Looking into the future, translation of adaptive optics ophthalmoscopy into clinical practice may facilitate early detection of microscopic retinal abnormalities that characterize these conditions. With conventional methods of physical examination, diagnosis of retinal diseases that may masquerade as neurological causes of vision loss can be challenging. Current advance in multimodal ophthalmic imaging along with electrophysiologic studies enhances the provider's ability to make early diagnosis and monitor progression of these conditions.

[Differential diagnosis of hydroxychloroquine-induced retinal damage]. / Differentsial'naya diagnostika porazheniya setchatki pri toksicheskom vozdeistvii gidroksikhlorokhina.

Coronavirus infection is currently en extremely relevant scientific topic due to the emergence of a new serotype that causes a condition identified as Severe Acute Respiratory Syndrome (SARS)-COV-2. Chloroquine and hydroxychloroquine have a long history of use against other infectious diseases, they are available and inexpensive, so the possibility of using them in vivo and in vitro to suppress the infectious agent was examined. Despite the noted therapeutic potential of these drugs, it was necessary to take into account the toxicological aspects that dictate the importance of rational use of 4-aminoquinoline derivatives. This review analyzes literature on the development patterns of hydroxychloroquine retinopathy, basic principles of diagnosis and differentiation of this condition from other types of retinal pathology.

Adverse ocular effects to systemic drug therapy / Szisztémás gyógyszerek szemészeti mellékhatásai

Systemic medications of various diseases can have adverse effects on the eye that range from asymptomatic lesions to potentially blinding complications such as toxic retinopathy and optic neuropathy. In the course of ophthalmological screening, with the early detection of toxic effects, the majority of drug-induced eye disorders can be prevented and even be reversed. Our review focuses on major drugs with common and significant ocular side effects. Physicians prescribing medications need to be keenly aware of ocular toxicity risks and the importance of regular screening. Orv Hetil. 2020; 161(23): 951-961.

Hydroxychloroquine dosing and toxicity: A real-world experience in Saudi Arabia of 63 patients.

PURPOSE: To assess the ocular toxicity in patients on high doses of hydroxychloroquine (HCQ) per weight, as per the latest American Academy of Ophthalmology (AAO) screening guidelines for HCQ toxicity. METHODS: This is a multi-center study looking at consecutive patients attending the ophthalmology clinics at a tertiary hospital and a private clinic in Saudi Arabia. A data collection sheet was used to collect patient's information regarding the dose per body weight, duration of HCQ use and any risk factors associated with the use of the medication as per the latest AAO guidelines for HCQ screening. Ancillary testing including fundus photography, automated visual field (10-2) and spectral domain ocular coherence tomography were done. Further testing with fundus auto-fluorescence and multifocal ERG were done when needed. The presence or absence of toxicity was recorded. RESULTS: A total of 63 patients were included in the study, 58 females and 5 males. The average patient age was 45 years (range 18-72). The mean dosage of HCQ was 3.9 mg/kg. Fourteen (22%) patients were on doses higher than 5 mg/kg. The duration of treatment ranged from 1-30 years (average 8.3). Thirty six (57%) patients were on the drug for more than 5 years. We found only one (1.58%) patient with HCQ toxic retinopathy over a mean of 8 years treatment period. CONCLUSION: A significant number of our patients were found to be on doses of >5 mg/kg of HCQ, which may put them at a higher risk for retinal toxicity. Low dose HCQ such as 100 mg tablets should be made available to help physicians in adjusting the dose as per the latest reported guidelines by the AAO.

Iodate induced toxic retinopathy: a case report.

BACKGROUND: Iodine deficiency is a common preventable cause of intellectual and developmental disabilities. Iodine in the form of potassium iodate is added to the common salt under the National Iodine Deficiency Disorder Control Program in India. Overdose of iodate can lead to retinal toxicity. CASE PRESENTATION: We hereby present a case of a 34 year old male patient who presented to us 10 years following iodate ingestion. There was widespread outer retinal atrophy, foveal atrophy and sub-retinal fibrosis noted on fundus evaluation. The fundus fluorescein angiogram was suggestive of window defects while the scotopic electroretinogram showed diminished amplitude pointing towards a grave prognosis. CONCLUSIONS: Excessive ingestion of potassium iodate can lead to outer retinal atrophy due to its toxicity to the retinal pigment epithelium and photo-receptors. The degree of damage is dependent on the ingested dose.

[Variability of chloroquine and hydroxychloroquine retinopathy among various ethnicities]. / Différences ethniques parmi les patients souffrant de toxicité maculaire aux antipaludéens de synthèse.

INTRODUCTION: Current screening recommendations for chloroquine (CQ) and hydroxychloroquine (HCQ) retinopathy are based on central 10°C static perimetry and a high-resolution SD-OCT with a special attention to the inferior part of the macula where the toxicity usually starts by ellipsoid zone disruption. However, Melles and Marmor, have recently shown a great variability in the topography of the initial toxicity observed among various ethnicities, which is important to keep in mind so as not to miss early toxicity in certain subgroups of patients. METHODS: Review of the literature. RESULTS: Ethnic differences have been shown regarding the topography of the initial retinal toxicity of CQ and HCQ, particularly between Caucasian and Asian subjects. In Caucasians, the first signs of toxicity are more often localized in the inferior para-foveal area associated with a decrease in retinal sensitivity in the upper 10°C visual field. However, in Asian subjects, the first signs of toxicity appear more pericentral (still inferior) with an extramacular pattern that could be missed by the usual 10°C visual field screening. DISCUSSION/CONCLUSION: The pathophysiology of these ethnic differences is unknown and may be due to distinct genetic predisposition to CQ and HCQ toxicity. Screening strategies should be adjusted to the ethnicity and performed in Asian subjects with larger visual fields (30°C), along with SD-OCT, looking for ellipsoid disruption≥8°C from the fovea. The recognition of this pericentral topography and an adjusted screening protocol should avoid late diagnosis in Asians treated with CQ and HCQ.

Docetaxel Retinopathy: A Case Report.

BACKGROUND: To report the use of En-face optical coherence tomography (OCT) in a patient treated with docetaxel and tamoxifen for breast cancer for the detection of macular edema (ME) without evidence of leakage on fluorescein angiography (FA). CASE PRESENTATION: A 52-year-old woman treated for breast cancer presented with bilateral visual loss for 2 months. FA showed no significant leakage while spectral-domain OCT scans of both eyes showed foveolar and parafoveolar cystic spaces in a moderately thickened macula. En-face OCT segmented at the inner retina showed the petaloid arrangement of cystic cavities, comparable to a cystoid ME. CONCLUSIONS: The combined use of tamoxifen could have potentiated the toxic effect of docetaxel on the macula. En-face OCT images may reveal a petaloid aspect of the macula due to cysts in the inner retina segmentation, when FA shows no leakage.

Assessment of hydroxychloroquine maculopathy after cessation of treatment: an optical coherence tomography and multifocal electroretinography study.

OBJECTIVE: This study was conducted to evaluate the macular status of patients treated with hydroxychloroquine before and after cessation of treatment. METHODS: Forty-two patients with systemic lupus erythematosus underwent ocular examination based on visual acuity evaluation, optical coherence tomography retinal thickness measurements, and multifocal electroretinography (mfERG) records at first visit. The tests were repeated 6 months after treatment withdrawal and compared to the findings at their first visit. RESULTS: Mean visual acuity (measured in log minimum angle of resolution) of both eyes was statistically increased after hydroxychloroquine discontinuation (difference in means: 0.06 [P<0.0001] and 0.01 [P=0.003] for the right and left eyes, respectively). Retinal response amplitudes of central and peripheral areas were significantly improved for both eyes. The following values were observed for central responses: the difference in means was -19.9 (P<0.0001) and -13.6 (P<0.0001) for the right eye and the left eye, respectively; for peripheral responses, difference in means was -10.3 (P<0.0001) and -9.5 (P<0.0001) for right eye and left eye, respectively, after the 6-month examination. There were no statistically significant differences in the retinal thickness of patients after cessation of treatment. The visual acuity of the patients was correlated to central and peripheral mfERG responses (r=-0.53 [P<0.0001] and r=-0.53 [P<0.0001], for the right eye and the left eye, respectively). CONCLUSION: The visual acuity of patients receiving hydroxychloroquine improves along with the amplitudes of the mfERG responses 6 months after discontinuation of the drug, but no difference in retinal thickness is identified.

Alterações oftálmicas associadas à intoxicação experimental por closantel em caprinos / Ophthalmic changes associated with the experimental poisoning by closantel in caprine

Alterações oftálmicas foram experimentalmente induzidas em caprinos após superdosagem com o anti-helmíntico closantel. Foram usados cinco caprinos com sete a oito meses de idade, produtos do cruzamento da raça Saanen com a Pardo Alpino. Os animais mostraram sinais de intoxicação entre quatro e cinco dias após a administração do closantel. Os sinais clínicos caracterizaram-se principalmente por distúrbios neurológicos centrais e cegueira. Ao exame clínico, observaram-se midríase bilateral, perda do reflexo pupilar à luz e cegueira bilateral. À oftalmoscopia indireta, foram observadas degeneração aguda de retina e papiledema. As alterações crônicas mostravam disco óptico acinzentado, atrofia de vasos e da retina. Nos fundos tapetal e não-tapetal notavam-se áreas de despigmentação e lesões irregulares castanho-amareladas. As alterações histológicas consistiam em perda dos neurônios da camada ganglionar e das células da camada nuclear interna e externa da retina. As alterações agudas no nervo óptico e na substância branca do encéfalo foram de degeneração espongiforme. As alterações crônicas do nervo óptico caracterizavam-se por extensa necrose e infiltração de células Gitter.

Ophthalmic alterations were experimentally induced after overdose with the anthelmintic closantel. Five seven to eight- months-old, Saanen x Alpine caprine were used. The animals showed clinical signs of toxicosis four to five days after the administration of closantel. Clinical signs were primarily characterized by central nervous disturbances and blindness. Clinically, bilateral mydriasis, loss of pupillary light reflex, and blindness were observed. At indirect ophthalmoscopic examination, there was acute retinal degeneration and papilledema. Chronic ocular changes consisted of paleness of the optic disc, vascular atrophy, and retinal atrophy. Areas of pigment loss and irregular yellowish-brown foci were present in the tapetal and non-tapetal fundus. Histological alterations consisted of neuronal loss in the ganglion cell layer and depletion of cells in both the outer and inner nuclear layers of the retina. Acute changes of spongy degeneration were noted in the optic nerve and in the cerebral white matter. Chronic lesions in the optic nerve were characterized by extensive necrosis and infiltration by Gitter cells.