Chloroquine and hydroxychloroquine retinopathy: how to follow affected patients

The retinopathy caused by antimalarials is well known. The differences between antimalarials and daily and cumulative doses are important factors in predicting the development of retinopathy. None of the commonly used tests alone are satisfactory for detecting early retinal changes. We recommend baseline color fundus photographs and automated central visual fields to follow these patients every nine to 12 months. Between these examinations, Amsler grid testing is adequate for screening for early defects.     

Chloroquine and hydroxychloroquine retinopathy-related risk factors in a Turkish cohort

To evaluate the role of previously reported risk factors on developing retinopathy in patients treated with chloroquine (CQ) and hydroxychloroquine (HCQ). Ophthalmologic examination, visual field testing, and spectral domain-optical coherence tomography were performed in 31 patients treated with CQ and HCQ. Toxicity diagnosis was proven by electrophysiological assessment. The risk factors reported by the American Academy of the Ophthalmology (AAO) were compared between patients with (n = 5) and without toxicity (n = 26) findings. Risk score was calculated for each patient. CQ daily overdose per actual body weight was significantly higher in affected patients. There was no statistically significant difference between groups concerning risk score, estimated cumulative dose of CQ, daily dose of HCQ and CQ per lean body weight, daily overdose of CQ per lean body weight and actual body weight (>3 mg/kg). The cumulative dose of HCQ was significantly higher in non-affected patients. The risk factors reported by the AAO might not be applicable to all CQ- and HCQ-treated patients. Different risk factors not yet reported may play a role in the development of CQ and HCQ retinopathy.     

Possible retinotoxic effect of carbamazepine

Two cases of retinopathy possibly caused by the antiepileptic drug, carbamazepine (Tegretol) are presented. Two female patients in middle age with epilepsy had been treated with carbamazepine for more than 7 years when they experienced sudden visual disturbances and reduction of visual acuity without known concomitant systemic toxic effects. Ophthalmoscopy, fundus colour photography and fundus fluorescein angiography disclosed in one patient discrete, and in the other patient extensive lesions of the retinal pigment epithelium in the posterior poles of the eyes including the macular regions. Discontinuation of carbamazepine led to improvement of visual function and of the morphological changes in the fundi of the patient with the most pronounced lesions. It is suggested that carbamazepine, a drug nearly chemically identical with the tricyclic psychotropic agents, might cause damage of the retinal pigment epithelium in long-term treatment. Further clinical controlled studies of the possible retinotoxic effect of this agent are, however, required.     

Association between higher cumulative doses of recombinant erythropoietin and risk for retinopathy of prematurity.

BACKGROUND: Retinopathy of prematurity is a complication of premature birth that varies in its severity. The incidence and severity of retinopathy of prematurity at our perinatal center in a regional referral hospital changed substantially during 1995 to 1998 and presented us with an opportunity to examine whether there was a protective effect on risk of retinopathy associated with exposure to recombinant erythropoietin. METHODS: We undertook a retrospective cohort study. From January 1995 through December 1998, charts of infants weighing<1500 g, who were 30 weeks' gestation or less, and who were admitted and survived to the first eye examination at 6 weeks were reviewed. Primary and secondary risk factors were recorded from the first 6 weeks of life. Of the eligible infants, 327 of 390 (84%) had complete records and retinal examinations. The probability for progression of retinopathy was estimated by logistic regression multivariate analysis using the continuation-ratio model. RESULTS: The overall incidence of retinopathy of prematurity was 36%. Recombinant erythropoietin exposure, as total 6-week dose, was independently associated with an increased risk for progression of retinopathy, OR=1.27 per 500 units/kg (95%CI=1.04, 1.55, P=0.02). Postnatal day of recombinant erythropoietin initiation also was associated with retinopathy risk but did not reach conventional statistical significance, OR=1.07 (CI=1.00, 1.14, P=0.07). CONCLUSIONS: These findings identify an association between cumulative recombinant erythropoietin exposure, used to reduce blood transfusions in premature infants, and an increased risk for retinopathy of prematurity. The nonhematopoietic properties of erythropoietin may account for the above findings, however further evaluation with confirmation is required.     

Ocular toxicity of hydroxychloroquine

This review summarizes the current literature regarding the ocular complications of hydroxychloroquine. Hydroxychloroquine has been used since the 1950s for the treatment of various rheumatic and dermatologic diseases. Hydroxychloroquine can cause ocular toxicity, with the most serious being an irreversible retinopathy. At the present time, no "gold standard" exists for identification of the ocular toxicity prior to its development. This has led to controversy regarding the recommendations for ophthalmologic examinations for screening patients on hydroxychloroquine.     

Ocular safety of hydroxychloroquine

Analysis of all published cases and Food and Drug Administration reports of retinopathy induced by hydroxychloroquine did not show any evidence of permanent visual-field scotomas occurring when the daily dose did not exceed 6.5 mg/kg body weight for maintenance therapy. Small risk factors may appear at this dosage level only when the duration of treatment exceeds ten years and/or chronic renal insufficiency is present. Because macular diseases not related to this drug commonly occur in older patients, periodic ophthalmologic examinations and central-field testing are recommended. A modified Amsler grid macular screening test is described, and participation of the treating physician in the testing program is encouraged to provide the maximum medicolegal protection.     

Chloroquine Retinopathy: Is Fluorescein Angiography Necessary?

Color fundus photographs and corresponding fluorescein angiograms from 83 patients suspected of having chloroquine retinopathy were reviewed in a retrospective masked study to determine the relative sensitivity of these two photographic methods in the diagnosis of retinal toxicity. We identified retinal toxicity on both color photographs and fluorescein angiograms in 7.6% of cases, on the color photographs but not on the corresponding angiograms in 6.1% of cases, and on the fluorescein angiograms but not on the color photographs in 1.5% of cases. Fluorescein angiography may not be as sensitive as color fundus photography (or ophthalmoscopy) in the diagnosis of chloroquine retinopathy.     

The cumulative normalised rim/disc area ratio curve

Background: The assessment of the cup of the optic disc depends, among other criteria, on the disc area. A small cup in a small optic disc can indicate an advanced glaucomatous lesion, while on the other hand a large cup in a large optic disc can be normal. Therefore, a cumulative normalised rim/disc area ratio curve could help to distinguish between glaucomatous and normal optic cups. The aim of our study was to calculate and to evaluate such a cumulative normalised rim/disc area ratio curve. Methods: Heidelberg Retina Tomograph examinations of the optic nerve head of 100 randomly selected eyes of 100 normal subjects were evaluated. We calculated the disc area-adjusted normalised rim/disc area ratio in sectors of 10°. The 95th, 90th and 50th percentiles of each of the 36 sectors were displayed in descending order. Results: In relation to the normal percentile curves, it is possible to display an individual normalised rim/disc area ratio curve. We obtained such curves for a normal optic disc, optic nerve heads with moderate and advanced lesions and a small optic disc with glaucomatous damage. Conclusion: We present a new display mode for the results of Heidelberg Retina Tomograph optic nerve head examination, which may be helpful for easy and reliable assessment of the local, diffuse and combined components of glaucomatous optic nerve head damage depending on optic disc size.     

Chloroquine retinopathy: pattern of presentation in Ibadan,Sub-Sahara Africa

Background

Self-medication with chloroquine is common in Ibadan, Sub-Sahara Africa. Retinopathy from chloroquine is not uncommon. The aim was to determine the pattern of presentation.

Methodology

Cases of Chloroquine retinopathy seen at the Retina and Vitreous Unit of the University College Hospital, Ibadan between 2008 and 2014 were reviewed. Information on age, sex, duration of chloroquine use, and visual loss were retrieved. Visual acuity at presentation, anterior, and posterior segment findings were documented. The results were analyzed using proportions and percentages.

Results

Fourteen cases were seen during the study period. Mean age was 50.7 years. Male to female ratio was 3.5 : 1. Average duration of visual loss before presentation was 2.7 years. Average duration of self-medication with chloroquine was 5.3 years. Presenting visual acuity showed 2(14%) cases of bilateral blindness(VA<3/60 in both eyes); 5(35.7%) cases of uniocular blindness; three cases of bilateral low vision(VA worse than 6/18 but better than 3/60). Anterior segment examination showed abnormal sluggish pupillary reaction in those with severe affectation. Dilated fundoscopy showed features ranging from mild macular pigmentary changes and bulls eye maculopathy to overt extensive retinal degeneration involving the posterior pole, attenuation of retinal vessels, optic atrophy, and beaten bronze appearance of atrophic maculopathy.

Conclusion

Chloroquine retinopathy is not uncommon in Ibadan, Sub-Sahara Africa. Bulls eye maculopathy, extensive retinal, and macular degeneration with optic atrophy are the main presentations. Public health education is imperative.     

An objective method of diagnosing hydroxychloroquine maculopathy

Background:Hydroxychloroquine (HCQ) maculopathy is irreversible; primary prevention is done by regular monitoring. Guidelines of the Royal College of Ophthalmologists identify definite toxicity as having abnormal results of two screening tests, we present a quantitative method for interpreting these guidelines.Methods:We obtained ocular coherence tomography (OCT) scans of 100 patients who have been on HCQ for 5 years or more (patients) and 70 age-matched controls. Both groups had 10’2 visual field (VF) test. We used linear regression to determine the cut-off points for each of the eight Early Treatment of Diabetic Retinopathy Study (ETDRS) macular sectors for the VF and OCT. We calculated the probability of developing maculopathy using logistic regression.Results:Mean patient age: 59.9 years, 85% females, no statistically significant age difference between the patients and the control groups. Diagnosis: 64% rheumatoid arthritis, 14% Sjogren’s syndrome, 16% systemic lupus and 6% various other rheumatology conditions. Mean duration of use was 6.3 years. Logistic regression results show strong negative correlation between the outer nuclear layer (ONL) volume and probability of toxicity. Goodness of fit was tested using Hosmer and Lemeshow test that indicates a high significance with a high P-value of 1.Conclusions:Combining the ONL volume reduction and VF retinal sensitivity reduction per each of the eight ETDRS macular sectors provides an accurate and objective way of diagnosing HCQ maculopathy, this helps busy eye units establishing an optometrist-led or virtual service because it is independent of the assessor’s level of experience.Subject terms: Diseases, Biological techniques     

Fundus autofluorescence and mfERG for early detection of retinal alterations in patients using chloroquine/hydroxychloroquine

PURPOSE: To evaluate and compare the value of fundus autofluorescence (FAF) imaging and multifocal electroretinography (mfERG) in early detection of retinal alterations in patients using chloroquine/hydroxychloroquine (CQ/HCQ). METHODS: FAF imaging was performed in a consecutive series of 25 patients with long-term CQ or HCQ treatment (duration, >1 year), with or without visual disturbances. In addition, mfERG was performed in accordance with ISCEV (International Society for Clinical Electrophysiology of Vision) guidelines in 23/25 patients. RESULTS: In 10/25 patients alterations of FAF were observed. Mild changes were limited to a pericentral ring of increased FAF. More advanced stages presented as pericentral mottled loss of FAF with increased FAF in the adjacent retina and later on a complete loss of pericentral FAF. In one case, a pericentral ring was observed when ophthalmoscopy and fluorescein angiography were normal. Marked progression of FAF abnormalities was observed during a 3-year follow-up in two of three patients. With the mfERG, pericentral, central, or generalized amplitude reductions were detected in all patients with FAF abnormalities and in an additional four patients with normal FAF. CONCLUSIONS: FAF imaging can be reliably used to detect early retinal pigment epithelial alterations in CQ/HCQ retinopathy. Ophthalmoscopy and fluorescein angiography appear to be less sensitive. With the mfERG, more retinal abnormalities were detected compared with FAF imaging.     

Ocular hypertension in patients with central/hemicentral retinal vein occlusions: cumulative prevalence and management

AIM: To prospectively evaluate the cumulative prevalence and the management of ocular hypertension (OH) in patients with unilateral acute central/hemicentral retinal vein occlusions (C/HCRVOs) over the course of 3y. METHODS: The study included 57 patients with unilateral acute C/HCRVOs. All patients underwent a comprehensive ophthalmological examination of both eyes. OH associated with C/HCRVO in patients showing a score >5% for the risk of conversion to primary open angle glaucoma (POAG) was treated with OH medication. The treatment aimed for a decrease in intraocular pressure (IOP) to <21 mm Hg with a >22% reduction from the initial values. The cumulative prevalence of OH and the effectiveness of treatment assessed by the cumulative prevalence of conversion from OH to POAG, were estimated. RESULTS: Fifteen patients had OH associated with C/HCRVOs, the cumulative prevalence of OH was 29.4% (95% confidence interval, 16.9-41.9). The mean value of the risk score of OH conversion to POAG for the 5 subsequent years was 11.7%±5.4%. The IOP significantly decreased from 25.67±2.16 mm Hg to 18.73±2.96 mm Hg. None of the OH patients converted to POAG during the follow-up period. CONCLUSION: The increased cumulative prevalence of OH in C/HCRVO patients indicates that OH is a risk factor for the appearance of venous occlusion. Patients with OH associated with C/HCRVO must be considered to be at high risk for conversion to POAG. Treatment with OH medications prevented conversion to POAG during the 3-year follow-up.