Recommendations on Screening for Chloroquine and Hydroxychloroquine Retinopathy (2016 Revision).

BACKGROUND: The American Academy of Ophthalmology recommendations on screening for chloroquine (CQ) and hydroxychloroquine (HCQ) retinopathy are revised in light of new information about the prevalence of toxicity, risk factors, fundus distribution, and effectiveness of screening tools. PATTERN OF RETINOPATHY: Although the locus of toxic damage is parafoveal in many eyes, Asian patients often show an extramacular pattern of damage. DOSE: We recommend a maximum daily HCQ use of ≤5.0 mg/kg real weight, which correlates better with risk than ideal weight. There are no similar demographic data for CQ, but dose comparisons in older literature suggest using ≤2.3 mg/kg real weight. RISK OF TOXICITY: The risk of toxicity is dependent on daily dose and duration of use. At recommended doses, the risk of toxicity up to 5 years is under 1% and up to 10 years is under 2%, but it rises to almost 20% after 20 years. However, even after 20 years, a patient without toxicity has only a 4% risk of converting in the subsequent year. MAJOR RISK FACTORS: High dose and long duration of use are the most significant risks. Other major factors are concomitant renal disease, or use of tamoxifen. SCREENING SCHEDULE: A baseline fundus examination should be performed to rule out preexisting maculopathy. Begin annual screening after 5 years for patients on acceptable doses and without major risk factors. SCREENING TESTS: The primary screening tests are automated visual fields plus spectral-domain optical coherence tomography (SD OCT). These should look beyond the central macula in Asian patients. The multifocal electroretinogram (mfERG) can provide objective corroboration for visual fields, and fundus autofluorescence (FAF) can show damage topographically. Modern screening should detect retinopathy before it is visible in the fundus. TOXICITY: Retinopathy is not reversible, and there is no present therapy. Recognition at an early stage (before any RPE loss) is important to prevent central visual loss. However, questionable test results should be repeated or validated with additional procedures to avoid unnecessary cessation of valuable medication. COUNSELING: Patients (and prescribing physicians) should be informed about risk of toxicity, proper dose levels, and the importance of regular annual screening.

Posterior segment toxicity after gemcitabine and docetaxel chemotherapy.

PURPOSE: To report outer retinal disruption and uveal effusion after gemcitabine and docetaxel combination therapy. CASE REPORT: A 78-year-old woman presented with blurry vision after two cycles of gemcitabine and docetaxel combination chemotherapy for stage IV sarcoma. At presentation, visual acuity was finger counting and 20/25 in the right and left eyes, respectively. Slit-lamp examination and B-scan ultrasonography revealed severe uveal effusion in the right eye and choroidal folds in the left eye. Spectral domain optical coherence tomography showed disruption of photoreceptor inner segment ellipsoid band in the right eye. The patient was monitored weekly with ophthalmic examination and B-scan ultrasonography, while continuing with gemcitabine monotherapy. At 8 weeks follow-up, uveal effusion improved considerably and visual acuity was 20/40 and 20/20 in the right and left eyes, respectively. CONCLUSIONS: Uveal effusion and outer retinal disruption were reported after gemcitabine and docetaxel chemotherapy. Early detection and close ophthalmic monitoring may allow concurrent cancer treatment and prevention of possible chemotherapy-induced ocular side effects.

Hemorrhagic Retinopathy after Spondylosis Surgery and Seizure.

PURPOSE: To report bilateral hemorrhagic retinopathy in an adult female subject after lumbar spinal surgery and seizure. CASE REPORT: A 38-year-old woman presented with bilateral blurry vision and spots in the visual field. The patient had lumbar spondylosis surgery that was complicated by a dural tear with persistent cerebrospinal fluid leak. Visual symptoms started immediately after witnessed seizure-like activity. At presentation, visual acuity was 20/100 and 20/25 in the right and left eye, respectively. Dilated fundus examination demonstrated bilateral hemorrhagic retinopathy with subhyaloid, intraretinal, and subretinal involvement. At 4-month follow-up, visual acuity improved to 20/60 and 20/20 in the right and left eye, respectively. Dilated fundus examination and fundus photography showed resolution of retinal hemorrhages in both eyes. CONCLUSIONS: The first case of bilateral hemorrhagic retinopathy after lumbar spondylosis surgery and witnessed seizure in an adult was reported. Ophthalmic examination may be warranted after episodes of seizure in adults.

Objective area measurement technique for choroidal neovascularization from fluorescein angiography.

The purpose of this study was to develop a non-biased method of quantitatively measuring choroidal neovascularization (CNV) areas based on late-phase fluorescein angiography (FA) images. Experimental CNV was induced in Long Evans rats by laser disruption of the Bruch's membrane. FA was performed weekly for 5weeks. Multi-Otsu thresholding (MOT) was used to quantify CNV in late-phase FA images from both experimental rodent CNV and wet age-related macular degeneration (wAMD) patients. Images were automatically thresholded into three levels based on the image histogram, with the highest level containing CNV. To determine the technique's ability to quantify CNV areas, rats were given either triamcinolone acetonide or dexamethasone sodium phosphate to treat CNV and compared to untreated rats. The rat CNV lesion areas measured from 5-week histology sections from each treatment group were compared to areas measured from the corresponding FA images. MOT was able to detect statistical decreases in rodent CNV area in the treatment groups versus control from weeks 3 through 5. The ratio of CNV area measured from histology to area measured from FA images was not statistically different between groups. Finally, to determine the usefulness of MOT on pathological morphologies of CNV, MOT was performed on late-phase FA images from patients with classic and diffuse CNV. The technique was able to segment classical CNV in wAMD patients, but performed poorly with diffuse CNV. MOT provides a robust, objective, and quantifiable area measurement of CNV lesion area in both experimentally-induced and pathological CNV. The results indicate that MOT could be a useful research tool in helping evaluate the effects of therapeutics on CNV growth.

The effect of glutathione as chain transfer agent in PNIPAAm-based thermo-responsive hydrogels for controlled release of proteins.

PURPOSE: To control degradation and protein release using thermo-responsive hydrogels for localized delivery of anti-angiogenic proteins. METHODS: Thermo-responsive hydrogels derived from N-isopropylacrylamide (NIPAAm) and crosslinked with poly(ethylene glycol)-co-(L-lactic acid) diacrylate (Acry-PLLA-b-PEG-b-PLLA-Acry) were synthesized via free radical polymerization in the presence of glutathione, a chain transfer agent (CTA) added to modulate their degradation and release properties. Immunoglobulin G (IgG) and the recombinant proteins Avastin® and Lucentis® were encapsulated in these hydrogels and their release was studied. RESULTS: The encapsulation efficiency of IgG was high (75-87%) and decreased with CTA concentration. The transition temperature of these hydrogels was below physiological temperature, which is important for minimally invasive therapies involving these materials. The toxicity from unreacted monomers and free radical initiators was eliminated with a minimum of three buffer extractions. Addition of CTA accelerated degradation and resulted in complete protein release. Glutathione caused the degradation products to become solubilized even at 37°C. Hydrogels prepared without glutathione did not disintegrate nor released protein completely after 3 weeks at 37°C. PEGylation of IgG postponed the burst release effect. Avastin® and Lucentis® released from degraded hydrogels retained their biological activity. CONCLUSIONS: These systems offer a promising platform for the localized delivery of proteins.

Outcomes of treatment of pediatric choroidal neovascularization with intravitreal antiangiogenic agents: the results of the KKESH International Collaborative Retina Study Group.

PURPOSE: To evaluate safety and clinical results of intravitreal antiangiogenic agents for choroidal neovascularization in pediatric patients. METHODS: Retrospective, multicenter, interventional case series. A total of 45 eyes of 39 pediatric patients with choroidal neovascularization of various etiologies were treated with intravitreal injection of antiangiogenic agents (1.25 mg per 0.05 mL of bevacizumab or 0.5 mg per 0.05 mL of ranibizumab). RESULTS: There were 24 girls and 15 boys with group median age of 13 years (range, 3-17 years). Mean follow-up period was 12.8 months (range, 3-60 months). Median visual acuity in terms of logarithm of the minimum angle of resolution at presentation and last follow-up was 0.87 and 0.7, respectively (P = 0.0003). Mean and median number of injections received over the follow-up period was 2.2 and 1, respectively. At the last follow-up, 22 eyes (48%) gained more than 3 lines of vision and 27 eyes (60%) had final visual acuity 20/50 or better. Nine eyes (20%) did not improve and had severe vision loss (20/200 or worse). CONCLUSION: Intravitreal antiangiogenic therapy for choroidal neovascularization in pediatric patients seems temporarily safe and effective in majority of affected eyes. Because of the rarity and character of this condition, it is unlikely that any clinical trials will soon take place to study this or other treatment option.

Intravitreal injection technique and monitoring: updated guidelines of an expert panel.

PURPOSE: To review evidence and provide updated guidelines on intravitreal (IVT) injection technique and monitoring. METHODS: A review of the published literature on IVT injection from 2004 to 2014 formed the basis for round table deliberations by an expert panel of ophthalmologists. RESULTS: The dramatic increase in the number of IVT injections has been accompanied by a comparable increase in evidence surrounding IVT practice patterns and techniques. The expert panel identified a number of areas that have evolved since publication of the original IVT injection guidelines in 2004, the most notable of which were a lack of evidence to support the routine use of pre-, peri-, and postinjection antibiotics to reduce the risk of endophthalmitis, and the role of aerosolized droplets containing oral contaminants from the patient and/or providers as a potential source of infection. The panel emphasized the continued importance of applying povidone-iodine to and avoiding eyelid contact with the intended injection site and needle. CONCLUSION: Updated guidelines on IVT injection technique and monitoring are proposed based on a review of published literature and expert panel deliberations.

Retinal neurovascular alteration in type 2 diabetes with renal impairment in association with systemic arterial stiffness.

BACKGROUND: Diabetic retinopathy (DR) patients should be alert for subclinical macroangiopathy. We aimed to investigate the association between retinal neurovascular alteration and systemic arterial stiffness in type 2 diabetes mellitus (type 2 DM) patients with varying degrees of renal impairment. METHODS: The study included 170 patients with confirmed diagnosis of type 2 DM aged ≥18 years old. Renal function was assessed by estimated glomerular filtration rate (eGFR). Arterial stiffness was measured by brachial-ankle pulse wave velocity (baPWV) and ankle brachial index (ABI). Retinal neurovascular parameters were derived from Optical Coherence Tomography (OCT)/OCT-Angiography, represented by vessel density (VD Central, Inner, Outer, Full), foveal avascular zone (FAZ area and FAZ perimeter) of the superficial capillary plexus, the average of macular ganglion cell-inner plexiform layer thickness (ave mGC-IPLt) and the average of retinal nerve fiber layer thickness (aveRNFLt). The association between variables among the groups (according to renal function, diabetic retinopathy (DR) severity, and arterial stiffness categories) were analyzed by regression analysis with multiple hypothesis testing commands. RESULTS: Out of the 265 eyes, the mean DM duration and HbA1c were 6.21 ± 6.37 years and 8.44 ± 2.06% respectively. While the mean of eGFR, baPWV and ABI were 66.78 ± 32.80 ml/min/1.73m2, 15.49 ± 3.07 m/s, and 1.05 ± 0.12, respectively. Patients with more severe renal impairment demonstrated longer DM duration (p < 0.001), higher baPWV (p < 0.0001), and retinal vascular alteration. Proliverative DR group showed the lowest eGFR (p < 0.0001), highest baPWV (p < 0.0001), and retinal neurovascular changes. Significantly lower eGFR and retinal vascular alteration were found in the baPWV > 14 group. Some neurovascular parameters were significantly negatively correlated with baPWV; moreover, retinal neurovascular changes were also noted in the abnormal ABI group. CONCLUSIONS: The strong association between changes in the retinal neurovascular system, DR severity, renal impairment, and arterial stiffness in type 2 DM was confirmed. Patients with more severe renal impairment had higher levels of arterial stiffness, more severe DR and retinal neurovascular alteration. Retinal neurovascular changes seen in OCT/OCTA might mimic renal microvascular alteration and systemic arterial stiffness. Therefore, assessment of baPWV and OCT/OCTA should be integrated in DR screening to enhance cardiovascular risk stratification and prognosis as well as to provide clinically useful early identification of subclinical micro- and macrovascular alterations.

Update on retinal detachment surgery.

PURPOSE OF REVIEW: Update on controversies in the surgical management of rhegmatogenous retinal detachment. RECENT FINDINGS: There are multiple new reports regarding the development and management of retinal detachment. Current use of oral fluoroquinolones may be associated with onset of retinal detachment, although the clinical relevance of this correlation is uncertain at this time and the finding has not been replicated in subsequent studies. Pars plana vitrectomy (PPV) continues to demonstrate efficacy as a primary treatment for retinal detachment, especially in pseudophakic patients. In many patients with macula-on retinal detachment, scheduling surgery after a short time delay is not necessarily deleterious and may actually be beneficial. Novel surgical tools, including bioerodible scleral buckling materials and artificial vitreous substitutes, are being investigated. SUMMARY: Retinal detachment remains an important cause of visual loss. Although current surgical techniques demonstrate high rates of anatomic and visual success, further advances will probably benefit patients with retinal detachment.

EIGHTY-TWO-YEAR-OLD MONOCULAR FEMALE WITH ACUTE DECREASED CENTRAL VISION.

PURPOSE: To present a case of suspected sympathetic ophthalmia in an 82-year-old monocular woman. METHODS: Case report. RESULTS: Here, we present an 82-year-old woman, status postcataract extraction with lens subluxation followed by a complicated course ultimately requiring enucleation because of a blind and painful eye in 2020, who developed contralateral choroidal lesions 6 months postenucleation along with vitritis and anterior uveitis. The lesions were suspicious for an infectious versus autoimmune etiology. Thorough systemic work-up and multimodal imaging suggest an autoimmune case. The findings in this patient suggest early identified sympathetic ophthalmia with multifocal choroiditis. This patient responded well to treatment of the acute episode with systemic corticosteroids and ultimately required steroid-sparing immunosuppression. CONCLUSION: Sympathetic ophthalmia is a rare entity classically observed after intraocular surgery and trauma. It may mimic many infectious and noninfectious uveitis entities. In this patient, sympathetic is a primary concern given her history and age of presentation with consideration for other uveitic entities.

The Impact of Systemic Medications on Retinal Function.

This study will provide a thorough review of systemic (and select intravitreal) medications, along with illicit drugs that are capable of causing various patterns of retinal toxicity. The diagnosis is established by taking a thorough medication and drug history, and then by pattern recognition of the clinical retinal changes and multimodal imaging features. Examples of all of these types of toxicity will be thoroughly reviewed, including agents that cause retinal pigment epithelial disruption (hydroxychloroquine, thioridazine, pentosan polysulfate sodium, dideoxyinosine), retinal vascular occlusion (quinine, oral contraceptives), cystoid macular edema/retinal edema (nicotinic acid, sulfa-containing medications, taxels, glitazones), crystalline deposition (tamoxifen, canthaxanthin, methoxyflurane), uveitis, miscellaneous, and subjective visual symptoms (digoxin, sildenafil). The impact of newer chemotherapeutics and immunotherapeutics (tyrosine kinase inhibitor, mitogen-activated protein kinase kinase, checkpoint, anaplastic lymphoma kinase, extracellular signal-regulated kinase inhibitors, and others), will also be thoroughly reviewed. The mechanism of action will be explored in detail when known. When applicable, preventive measures will be discussed, and treatment will be reviewed. Illicit drugs (cannabinoids, cocaine, heroin, methamphetamine, alkyl nitrite), will also be reviewed in terms of the potential impact on retinal function.

Radiation Retinopathy and Benign Lymphoproliferative Orbital Tumor Presenting 47 Years Following Treatment of Hereditary Retinoblastoma.

PURPOSE: To better understand onset of radiation retinopathy and secondary orbital tumors in the setting of retinoblastoma treated with radiation and chemotherapy. METHODS: Case report. RESULTS: Here we present a 48-year-old female with a history of bilateral hereditary retinoblastoma status-post enucleation of the left eye and radiation therapy to the right eye, along with systemic chemotherapy. She underwent bladder leiomyosarcoma resection at age 24. In 2020, she presented with significantly delayed radiation retinopathy complicated by cystoid macular edema, and bevacizumab injections were initiated. An incidental benign lymphoproliferative tumor in the right lacrimal gland was found on B-scan ultrasound and was successfully excised. CONCLUSION: It is rare for radiation retinopathy to present with significant delay after local radiation treatment, with only 2 other cases found in the literature describing a similar late onset. In addition, there have been no other published cases of a secondary benign lymphoproliferative tumor in the setting of retinoblastoma treated with radiation and chemotherapy.

Novel Drug Delivery Methods and Approaches for the Treatment of Retinal Diseases.

This review discusses emerging approaches to ocular drug delivery for retinal diseases. Intravitreal injections have proven to be an effective, safe, and commonly used drug delivery method. However, the optimal management of chronic retinal diseases requires frequent intravitreal injections over extended periods of time. Although this can be achieved in a clinical trial environment, it is difficult to replicate in routine clinical practice. In addition, frequent treatment increases the risk of complications, incurs more costs, and increases the treatment burden for patients and caregivers. Given the aging global population and diabetes pandemic, there is an urgent need for drug delivery methods that support more durable retinal therapy while maintaining the efficacy and safety of currently available intravitreal therapies. Several innovative drug delivery methods are currently being investigated. These include sustained-release implants and depots using prodrugs, microparticles, and hydrogels, surgically implanted reservoirs, gene therapy via submacular injections or suprachoroidal injections, as well as topical and systemic therapies.

Fluorescein videoangiography data analysis protocol for mapping retinal vascular permeability in humans.

Fluorescein video angiographies (FVAs) are a diagnostic tool for eye diseases, such as diabetic retinopathy (DR). Currently, kinetic tracer model methods based on indicator-dilutions theory use FVAs to extract biomarkers (e.g., volumetric blood flow and retinal vascular permeability) via pixel mapping using two-step non-linear least square fitting. Prior to biomarker extraction, the FVAs must attain optimal quality. The objective of this research is to create a program to remove all frames experiencing signal drops (causes include blinking, squinting, and head movement). 15 FVAs (6 healthy control subjects, 6 diabetes mellitus no DR (DMnoDR) subjects, and 3 mild non-proliferative DR (NPDR) subjects) were analyzed for low quality frames. The average signal of each frame was analyzed as top, middle, and bottom thirds. The frame with maximum average signal up to the final frame of a created "Gold Standard" was compared with the raw AVI's frame with maximum average signal and subsequent frames. All frames before maximum average signal and any remaining frames were compared with the previous good-quality raw frame to determine if the frame of interest was of good quality. All remaining frames were subsequently re-evaluated and flagged if they had a local minimum prominence of 10% of the maximum average signal. The flagged frames', as well as former and subsequent frames', quality were subjectively determined. The AVI quality was subsequently tested via pre-DTKM processing and biomarker extraction via DTKM methods. Results displayed that the semi-automated frame removal process provides sufficient quality AVIs.

En face spectral-domain optical coherence tomography outer retinal analysis and relation to visual acuity.

PURPOSE: To describe a method of en face visualization and quantification of the photoreceptor inner segment/outer segment junction area, using spectral-domain optical coherence tomography, and association with visual acuity. METHODS: Case series of 74 eyes in 53 patients. Central 1-mm and 400-µm en face areas were analyzed with a computer algorithm. RESULTS: The presence or absence of inner segment/outer segment junction was visible on both spectral-domain optical coherence tomography en face and retinal cross sections. Thirty eyes (40.6%) had no retinal pathology and an average logMAR visual acuity of 0.116. Twenty-five eyes (33.8%) had intraretinal edema, with visual acuity of 0.494. Nineteen eyes had nonneovascular age-related macular degeneration (dry age-related macular degeneration, 25.6%), with visual acuity of 0.392. In all eyes, central 1-mm and 400-µm en face areas were 58.3 ± 25.0% and 56.4 ± 26.0%, which showed significant correlation with visual acuity (Pearson correlation, r = -0.66 and -0.56, both P < 0.001). This correlation was greater than correlation of visual acuity with central subfield thickness (r = 0.39, P < 0.001), macular volume (r = 0.36, P = 0.002), and average macular thickness (r = 0.37, P = 0.001). However, no variables were significantly correlated with dry age-related macular degeneration eyes. CONCLUSION: Central en face inner segment/outer segment junction areas are significantly correlated with visual acuity in most eyes. This may correlate better with visual acuity than other spectral-domain optical coherence tomography values, as a reflection of photoreceptor integrity. Dry age-related macular degeneration may disrupt the plane used to formulate the en face display. Advancements in spectral-domain optical coherence tomography may provide routine en face visualization analysis.

DEVELOPMENT OF CHOROIDAL NEOVASCULARIZATION AFTER TREATMENT WITH PHOTODYNAMIC THERAPY IN A 5-YEAR-OLD FEMALE WITH CHOROIDAL OSTEOMA.

PURPOSE: To describe a patient with a choroidal osteoma treated with photodynamic therapy to prevent tumor growth in whom choroidal neovascularization (CNV) developed after being treated with photodynamic therapy. METHODS: Case report. RESULTS: A 5-year-old Hispanic woman presented with an asymptomatic choroidal osteoma, temporal to the macula of her right eye. According to the patient's mother, her medical, surgical, and family history was unremarkable. At examination, best-corrected visual acuity was 20/30 in both eyes. After 11 months of follow-up, signs of tumor growth toward the fovea without any signs of CNV was noted. Photodynamic therapy was performed to prevent invasion of the foveola. Two months thereafter, the patient developed CNV in the macula region in the right eye, decreasing visual acuity to 20/200. The patient was treated with four total intravitreal injections of 1.25 mg of bevacizumab over 24 weeks, which resulted in inactivation of the CNV and improved visual acuity to 20/20. Choroidal neovascularization had been never reported in her past history and her follow-up visits over 7 years. In addition, no evidence of recurrent neovascular activity or tumor growth was reported. CONCLUSION: Choroidal osteoma is a benign tumor that can result in vision-threatening complications, caused by tumor growth and tumor decalcification. Photodynamic therapy is an effective modality in inducing choroidal osteoma decalcification and stabilization; however, CNV due to reperfusion following photodynamic therapy can be seen in the retina.

Simultaneous Release of Aflibercept and Dexamethasone from an Ocular Drug Delivery System.

PURPOSE: Intravitreal injections of anti-vascular endothelial growth factors (anti-VEGF) are the current standard of care for patients with choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). There is a growing subset of patients that does not respond to anti-VEGF monotherapy treatment. Some patients, however, do respond to combination therapy of corticosteroids and anti-VEGF. This treatment requires monthly/bimonthly injections of anti-VEGF and semi-annual injections of corticosteroid. A drug delivery system (DDS) that simultaneously releases multiple drugs could benefit these patients by reducing the number of injections. The purpose of this study was to characterize the simultaneous release of aflibercept and dexamethasone from a biodegradable microparticle- and nanoparticle-hydrogel DDS. METHODS: Dexamethasone-loaded nanoparticles and aflibercept-loaded microparticles were created using modified single- and double-emulsion techniques, respectively. Then, microparticles and nanoparticles were embedded into a thermoresponsive, biodegradable poly(ethylene glycol)-co-(L-lactic acid) diacrylate (PEG-PLLA-DA)-N-isopropylacrylamide (NIPAAm) hydrogel DDS. Drug release studies and characterization of DDS were conducted with varying doses of microparticles and nanoparticles. RESULTS: The combination aflibercept-loaded microparticle- and dexamethasone-loaded nanoparticle- hydrogel (Combo-DDS) achieved a total release time of 224 days. Small decreases were seen in swelling ratio and equilibrium water content for Combo-DDS compared to monotherapy aflibercept-loaded microparticle-hydrogel DDS (AFL-DDS) and monotherapy dexamethasone-loaded nanoparticle-hydrogel DDS (DEX-DDS). Bioactivity of aflibercept was maintained in Combo-DDS compared to AFL-DDS. CONCLUSIONS: The Combo-DDS was able to extend and control the release of both aflibercept and dexamethasone simultaneously from a single DDS. This may eliminate the need for separate dosing regiments of anti-VEGF and corticosteroids for wet AMD patients.

Optimizing the protocol for retinal vascular permeability mapping from fluorescein videoangiography data.

An intact blood-retinal barrier is critical to maintaining the function of the retina. Many diseases of the eye have been directly associated with impairment in vascular permeability, and methods to measure vascular permeability could offer a window into early detection of disease; however, there exist no direct measures of vascular permeability that have be translated to the clinic. This work details a complete clinical workflow to quantify vascular permeability and volumetric blood flow from fluorescein videoangiography data, with validation through realistic simulations. For optimizing the protocol, this study carried on frame rate of fluorescein videoangiography to generate a high-resolution image while minimizing the error.

Revised recommendations on screening for chloroquine and hydroxychloroquine retinopathy.

BACKGROUND: The American Academy of Ophthalmology recommendations for screening of chloroquine (CQ) and hydroxychloroquine (HCQ) retinopathy were published in 2002, but improved screening tools and new knowledge about the prevalence of toxicity have appeared in the ensuing years. No treatment exists as yet for this disorder, so it is imperative that patients and their physicians be aware of the best practices for minimizing toxic damage. RISK OF TOXICITY: New data have shown that the risk of toxicity increases sharply toward 1% after 5 to 7 years of use, or a cumulative dose of 1000 g, of HCQ. The risk increases further with continued use of the drug. DOSAGE: The prior recommendation emphasized dosing by weight. However, most patients are routinely given 400 mg of HCQ daily (or 250 mg CQ). This dose is now considered acceptable, except for individuals of short stature, for whom the dose should be determined on the basis of ideal body weight to avoid overdosage. SCREENING SCHEDULE: A baseline examination is advised for patients starting these drugs to serve as a reference point and to rule out maculopathy, which might be a contraindication to their use. Annual screening should begin after 5 years (or sooner if there are unusual risk factors). SCREENING TESTS: Newer objective tests, such as multifocal electroretinogram (mfERG), spectral domain optical coherence tomography (SD-OCT), and fundus autofluorescence (FAF), can be more sensitive than visual fields. It is now recommended that along with 10-2 automated fields, at least one of these procedures be used for routine screening where available. When fields are performed independently, even the most subtle 10-2 field changes should be taken seriously and are an indication for evaluation by objective testing. Because mfERG testing is an objective test that evaluates function, it may be used in place of visual fields. Amsler grid testing is no longer recommended. Fundus examinations are advised for documentation, but visible bull's-eye maculopathy is a late change, and the goal of screening is to recognize toxicity at an earlier stage. COUNSELING: Patients should be aware of the risk of toxicity and the rationale for screening (to detect early changes and minimize visual loss, not necessarily to prevent it). The drugs should be stopped if possible when toxicity is recognized or strongly suspected, but this is a decision to be made in conjunction with patients and their medical physicians.