Perifoveal retinal thickness changes after intravitreal aflibercept injection for choroidal neovascularization in age-related macular degeneration.

OBJECTIVE: There has been some concern that anti-vascular growth factor treatment accelerates the development of macular atrophy in eyes with neovascular age-related macular degeneration. During the treatment with aflibercept, the thickness of choroid may decrease. This may lead to photoreceptor death. The rod cells are more susceptible to atrophic changes than cones during the disease. We aimed to find any thickness changes in the perifoveal outer nuclear layer, where the highest density of rods is found, during the aflibercept intravitreal injection therapy. MATERIALS AND METHODS: Retrospectively, forty-two patients who were treated for age-related macular degeneration with choroidal neovascularization were included in the study. After the first three loading doses, intravitreal injections were repeated every two months. Outer nuclear layer thicknesses were measured 2000 µm away from the center of the fovea with OCT, at a total of 20 points, located at 180 and 90°. The mean of these measurements was obtained before the treatment and 1 year after the therapy. Results were compared by using the Wilcoxon Rank Test. RESULTS: The mean visual acuity was 1,11±0,287 logMAR at the beginning and increased to 0,53±0,32 LogMAR after. Perifoveal thickness was significantly reduced when compared with the thickness before the treatment (p = 0.039, p < 0.05). This result was also significantly lower than the control group thicknesses (p = 0.035, p < 0.05). CONCLUSION: Anti-VEGFs can cause loss of phagocytic functions of RPE. The mechanism of the observed thinning of the ONL may be described as follows: VEGF emitted by the RPE normally helps to maintain the choriocapillaris. Thus, injecting an anti-VEGF intravitreally causes RPE atrophy, which leads to a decrease in the choroidal vascular index. This in turn causes first the rods, and later the cones, that are part of the outer nuclear layer, to start to die and disappear, hence the thinning of this layer. As aflibercept consists of parts of the extracellular domain of both the VEGFR1 and VEGFR2 receptors, that are held together by a human IgG1 backbone, this makes the binding of aflibercept to VEGF-A and VEGF-B stronger as compared to the binding of the previously used ranibizumab or bevacizumab (by nearly a factor 100 in the case of the most abundant isoform VEGF-A 165). Besides, aflibercept also binds very well to placental growth factor (PIGF), which is also associated with several ocular diseases.

FOVEAL MÜLLER CELL CONE AS A PROGNOSTIC OPTICAL COHERENCE TOMOGRAPHY BIOMARKER FOR INITIAL RESPONSE TO ANTIVASCULAR ENDOTHELIAL GROWTH FACTOR TREATMENT IN CYSTOID DIABETIC MACULAR EDEMA.

PURPOSE: To investigate the effect of the foveal Müller cell cone structure on the anatomical and functional response to intravitreal bevacizumab treatment in patients with diabetic macular edema. METHODS: In 93 treatment-naive eyes with center-involved cystic type diabetic macular edema, spectral-domain optical coherence tomography scans of baseline were retrospectively evaluated to determine the foveal Müller cell cone structure and prognostic features including length of disorganization in the retinal inner layers and ellipsoid zone disruption. The area and circularity of the foveal avascular zone of the superficial and deep capillary plexus 1 month after intravitreal bevacizumab treatment were evaluated using optical coherence tomography angiography. RESULTS: Destruction of the foveal Müller cell cone structure and a large foveal avascular zone in the deep capillary plexus (mm2) correlated strongly with a poor anatomical response (CST > 250 µm) at 1 month after first intravitreal bevacizumab (Exp [B] = 29.444, P = 0.002 and Exp [B] = 12.419, P = 0.013, respectively). A destroyed Müller cell cone structure (P = 0.008) and length of ellipsoid zone disruption (P < 0.001) at baseline were associated with poor visual acuity at 1 month after the first intravitreal bevacizumab. CONCLUSION: The foveal Müller cell cone structure correlates with the response to initial antivascular endothelial growth factor treatment.

Early Postnatal Oxygen Exposure Predicts Choroidal Thinning in Neonates.

Purpose: To evaluate whether choroidal thickness (CT) using arm-mounted optical coherence tomography (OCT) in infants screened for retinopathy of prematurity (ROP) correlates with oxygen exposure in neonates. Methods: OCT images were obtained in infants screened for ROP in a single level IV neonatal intensive care unit. CT was measured at three different locations: the subfoveal center and 1.5 mm from the fovea center in each direction. Correlation and regression analyses were performed to determine the relationship between clinical factors and CT. Clinical factors included gestational age, birth weight, presence of bronchopulmonary dysplasia (BPD), and fraction of inspired oxygen (FiO2) at defined time points: 30 weeks postmenstrual age (PMA), 36 weeks PMA, and on day of imaging. Results: Mean subfoveal, nasal, and temporal choroidal thicknesses CT (SFCT, NCT, and TCT, respectively) were 228.0 ± 51.4 µm, 179.7 ± 50.3 µm, and 186.4 ± 43.8 µm, respectively. SFCT was found to be significantly thicker than NCT and TCT (P < 0.0001 and P = 0.0002, respectively), but no significant difference was found between NCT and TCT (P = 0.547). Compared with infants without BPD, infants with BPD had thinner SFCT and NCT (P = 0.01 and P = 0.0008, respectively). Birth weight was positively correlated with SFCT (r = 0.39, P = 0.01) and NCT (r = 0.33, P = 0.045) but not TCT. Gestational age and ROP stage were not significantly associated with CT. SFCT was found to be significantly thinner with higher average FiO2 supplementation levels at 30 weeks PMA (r = -0.51, P = 0.01) but not at 36 weeks PMA. Regression analysis revealed that FiO2 at 30 weeks PMA was an independent predictor of SFCT in infants screened for ROP (P = 0.01). Conclusions: Early postnatal exposure (<32 weeks PMA) to higher oxygen supplementation in premature neonates statistically predicts choroidal thinning.

Resolution of bilateral foveal cysts in dome-shaped macula after treatment with topical dorzolamide.

Dome-shaped macula (DSM) is characterised by a convex anterior bulging of the macular area. It can further get complicated by accumulation of subretinal fluid (SRF). Foveal cysts that are bilateral, in a setting of DSM, are an entity not yet reported. Management options for DSM with SRF showed variable success. Topical carbonic anhydrase inhibitors (CAIs) have been successful in treating certain macular pathologies. The authors report a rare case of bilateral intraretinal foveal cyst in a myopic child with DSM with favourable response to topical dorzolamide. Topical CAIs may be considered a safe and effective option in such cases.

Direct and crossover effects of Phenylephrine and Cyclopentolate on foveal avascular zone and vessel density of macular capillary plexuses: an optical coherence tomography angiography study.

Purpose: To determine the influence of phenylephrine and cyclopentolate on foveal avascular zone (FAZ) and vessel density of macular capillary plexus measurements via optical coherence tomography angiography (OCTA). Materials and Methods: The participants were separated into 2 groups according to the administration of drops. One drop of phenylephrine 2.5% was administered on one eye of each subject in the phenylephrine group (n=30) and one drop of cyclopentolate 1% in the cyclopentolate group (n=30). FAZ parameters and vessel density values of both superficial (SCP) and deep capillary plexuses (DCP) were calculated via OCTA priorly and at 45 min following the drop administration in both eyes. Vessel density, acircularity index of FAZ, FAZ area, perimeter of FAZ and foveal density-300 were evaluated via OCTA. Results: The vessel density values of fovea in SCP and DCP was 18.51±7.14% and 36.05±8.76% and significantly decreased to 16.16±6.26% and 33.29±9.47% respectively after drop instillation in dilated eyes in phenylephrine group (p=0.041 and p=0.032). Likewise, the vessel density values in SCP and DCP were 21.56±7.74% and 39.27±8.76% and significantly decreased to 18.89±7.32% and 35.36±5.75% respectively, after drop instillation in dilated eyes in cyclopentolate group (p=0.035 and p=0.028). However, there was no significant difference between before and after instillation of drops in terms of foveal density-300 value via FAZ assessment tool in both dilated and nondilated contralateral eyes in both groups (p>0.05 for all). Conclusions: Mydriasis with phenylephrine and/ or cyclopentolate did not affect the foveal density-300 values while analyzing the perfusion of macula. Vessel density in foveal region should be evaluated via FAZ evaluation software of the OCTA.

Vascular density in age-related macular degeneration after one year of antiVEGF treatment with treat-and-extend and fixed regimens.

Treatment of neovascular age-related macular degeneration (nAMD) with VEGF can be performed with several posologies. The purpose of our cross-sectional study was to analyze retinal vessel density by quantitative OCT-angiography (OCT-A) and to compare treat-and-extend (T&E) and fixed treatment protocols to a control group with dry AMD. Altogether 48 patients were enrolled: 13 eyes with T&E protocol ranibizumab treatment (group A) and 17 eyes with fixed regimen aflibercept therapy (group B), the control group comprised 18 eyes with dry AMD (group C). One year after the start of the treatment, quantitative OCT-A (AngioVue-Optovue, Fermont, USA) was performed: superficial and deep retinal vessel densities were analyzed in the foveal and parafoveal regions. Our results show, that the density of retinal superficial vasculature in the fovea was not different between the treatment groups (A: 25.9±9.1%; B: 24.3%±8.9), neither from group C (25.6±4.8%). Superficial parafoveal vascular density of the retina, however, was decreased in both treated groups (A: 46.7±9.1%, B: 42.9±6.1%, C: 49.7±4.9%). In the deep retinal plexus, vascular density was lower in both treatment groups compared to that of in controls in both the foveal and parafoveal area (A: 29.8±6.3%, B: 32.5±6.9%, C: 36.4±1.7% and A: 46.3±3.8%, B: 47.1±5.3%, C: 49.7±4.9%, foveal and parafoveal respectively). Our data suggest, that after one year of anti-VEGF treatment, reduced macular vessel density in three of the four examined vascular regions can be found independent of the treatment regimen.

[Dexamethasone intravitreal implant (Ozurdex) in patients with diabetic macular edema: Real life safety and efficacy]. / Implant de dexaméthasone (Ozurdex) dans l'œdème maculaire diabétique : efficacité, et sécurité d'utilisation en vraie vie.

PURPOSE: The goal of this study was to investigate the safety and efficacy of the intravitreal dexamethasone implant (DI) for patients with diabetic macular edema (DME) in real life. METHODS: We conducted a monocentric retrospective analysis of the change in visual acuity and central macular thickness (CMT) after intravitreal injection of the DI at peak efficacy (2 months after injection) as well as the timing of reinjections and complications in patients with a loss of vision due to DME. RESULTS: Forty eyes of 33 patients were included, with a mean follow-up of 12.6 months. Thirty percent of the eyes experienced an increase in best corrected visual acuity (BCVA)>15 letters at peak efficacy (P<0.05) after each ID injection. Treatment-naive patients had a sustained response after Ozurdex injection, with better visual acuity at 3 months (P=0.02) and 4 months (P=0.04) than non-naïve patients and better visual acuity at 6 months despite identical baseline visual acuity (P<0.05). Anatomical efficacy was good, with approximately 60% of patients with CMT<300 microns at peak efficacy after each injection of ID. Thirty percent of eyes demonstrated ocular hypertension (OHT)>25mmHg at peak efficacy, and 12.5% of eyes required cataract surgery during follow-up. CONCLUSION: The DI has good functional and anatomic efficacy in these patients, with a good safety profile. Treatment-naïve patients with more recent DME had a more sustained increase in visual acuity after the injections and better visual recovery at 6 months. This encourages us to initiate DI therapy early if there is no response to anti-vascular endothelial growth factor (anti-VEGF) treatment.

Foveal Microvascular Structures in Eyes with Silicone Oil Tamponade for Rhegmatogenous Retinal Detachment: A Swept-source Optical Coherence Tomography Angiography Study.

Silicone oil (SO) is widely used as a long-term intravitreal tamponading agent for rhegmatogenous retinal detachment (RRD) repair. This study investigated the structural changes of the foveal microvasculature using optical coherence tomography angiography (OCTA) in patients with RRD treated with vitrectomy and SO tamponade. Thirty-eight patients with unilateral RRD who were treated with vitrectomy and SO tamponade and were followed up for ≥3 months after SO removal were included. En face OCTA images were obtained and foveal avascular zone (FAZ) area and vascular density (VD) were compared between study eyes and unaffected contralateral eyes. The FAZ area in deep capillary plexus (DCP) was larger (P < 0.001) and the VD in DCP was lower (P = 0.022) in the study eyes than in the fellow eyes. The duration of SO tamponade was significantly correlated with the enlargement of FAZ area (P = 0.034) and reduction of VD in DCP (P = 0.015). These changes could reflect vascular insufficiency in eyes with SO tamponade and may represent a potential explanation for the pathogenesis of retinal thinning and unexplained visual loss.

Serum pro-inflammatory factors as predictors of persistent diabetic macular oedema with limited anatomic response to anti-VEGF: association with intravitreal injection treatment profiles in real-world setting.

PURPOSE: To study the role of serum levels of pro-inflammatory factors in the identification of persistent diabetic macular oedema (DME) cases with limited anatomic response to anti-VEGF. Additionally, possible predictive associations between serum factors and intravitreal treatment profiles were analysed. METHODS: Cases with DME were treated with monthly bevacizumab (BVZ). After the sixth month of follow-up, if the change in central foveal thickness (CFT) was <20% of baseline, combination treatment with triamcinolone was initiated. All cases underwent a baseline laboratory workup including inflammatory, metabolic and prothrombotic factors. The following outcome parameters were evaluated: percentage of CFT change from baseline, occurrence of persistent DME with <20% change in CFT, achieving CFT <330 µm with ≤6 BVZ injections, total number of intravitreal injections (IVI), number of IVI after the 6th month and number of triamcinolone acetonide (TCA) injections. RESULTS: A total of 58 cases were included receiving a mean of 7.23 ± 1.55 IVI in 12 months, resulting in a significant improvement of visual acuity (VA) and CFT. No significant differences were found for baseline CFT, baseline LogMAR VA, diabetic retinopathy grade, age or duration of DM2 between cases initiating TCA and those treated only with anti-VEGF. Significant correlations were found between total number of IVI and the following serum factors: high-sensitivity C-reactive protein (hsCRP) (p = 0.004, r = 0.395), creatinine (p = 0.023, r = 0.338) and homocysteine (p = 0.037, r = 0.309). Regression analysis revealed that hsCRP was a significant predictor of TCA treatment (p = 0.028, r2  = 0.350). Cases requiring ≤6 IVI had significantly lower values of hsCRP (1.33 ± 1.07 versus 2.46 ± 2.18 mg/l, p = 0.016) and creatinine (0.71 ± 0.28 versus 0.94 ± 0.19 mg/dl, p = 0.003). CONCLUSIONS: Serum markers of microvascular damage (hsCRP, homocysteine and creatinine) were associated with a higher frequency of IVI due to persistent DME, suggesting a role for such biomarkers in the identification of limited responders to anti-VEGF monotherapy.

Structural and Functional Characterization of the Retinal Effects of Hydroxychloroquine Treatment in Healthy Eyes.

PURPOSE: To evaluate the influence of hydroxychloroquine in visual field and retinal layer thickness. METHODS: This is a retrospective cross-sectional study. Patients taking hydroxychloroquine without signs of hydroxychloroquine retinopathy were included. Optical coherence tomography segmentation was used to obtain the ETDRS map thickness of each retinal layer. Groups were divided into short-term (< 5 years) and long-term (≥5 years) drug use. RESULTS: We included 93 eyes of 93 patients (short-term: 25 eyes; long-term: 68 eyes). The inner nuclear layer (INL) was thinner in the long-term group (32.86 ± 2.12 vs. 34.14 ± 2.37 µm; p = 0.014). Considering long-term cases, the parafoveal ganglion cell layer (GCL) showed an inverse correlation with cumulative dose (r = -0.37; p < 0.001). After adjusting for confounders, parafoveal ganglion cell complex thickness was associated with cumulative dose (ß = -0.239; p = 0.011). The parafoveal outer retina and visual field indices were similar between groups and did not correlate with cumulative dose. CONCLUSION: Hydroxychloroquine leads to progressive thinning of the parafoveal inner retina, particularly the INL and GCL. Visual field indices do not reflect the long-term effects of the drug.

Correlation between redefined optical coherence tomography parameters and best-corrected visual acuity in non-resolving central serous chorioretinopathy treated with half-dose photodynamic therapy.

PURPOSE: To assess parameters on optical coherence tomography (OCT), and their correlation with best-corrected visual acuity (BCVA) in patients with non-resolving central serous chorioretinopathy (CSC). METHODS: For 25 non-resolving CSC patients treated with photodynamic therapy (PDT), the thickness of retinal layers was assessed on the foveal spectral-domain (SD) OCT scan. Evaluated OCT parameters included the central retinal thickness (CRT), defined as the internal limiting membrane (ILM) to ellipsoid zone (EZ) distance, and the second band thickness (SBT), defined as the EZ to hyperreflective subretinal accumulation distance. Integrity of the external limiting membrane (ELM) and the EZ bands was also determined. These parameters, along with BCVA and CRT measured automatically by SD-OCT device software were obtained before PDT, after PDT, and at final visit. After Bonferroni correction, a p-value <0.007 was considered statistically significant. RESULTS: Twenty-five patients could be included at last visit before PDT and first visit after PDT. At final visit, 24 patients could be included, since 1 patients was lost to follow-up. Mean CRT was 112 µm at last visit before PDT, 118 µm at first visit after PDT (p = 0.030), and 127 µm at final visit (p<0.001compared to baseline). Mean SBT was 74 µm, 26 µm (p<0.001 compared to baseline), and 21 µm (p<0.001 compared to baseline), respectively. Mean BCVA in Early Treatment of Diabetic Retinopathy Study letters was 79 at baseline, 85 at first visit after PDT (p = 0.005 compared to baseline), and 87 at final visit (p = 0.001 compared to baseline). BCVA had an estimated correlation of ß = 0.103 (p = 0.114) with CRT, ß = -0.051 (p = 0.014) with SBT, ß = 0.615 (p = 0.600) with the integrity of the ELM, and ß = 4.917 with the integrity of the EZ (p = 0.001). CONCLUSIONS: In non-resolving CSC patients treated with half-dose PDT, the CRT increased at final visit in comparison to the last visit before PDT. The continuity of the EZ on SD-OCT was positively correlated with BCVA. We propose that the distance between ILM and EZ should be used as a reliable CRT measurement in non-resolving CSC patients treated with half-dose PDT.

Effect of Latanoprost on Choroidal Thickness.

PURPOSE: The purpose of this study was to evaluate the changes in choroidal thickness during the use of latanoprost eyedrops which shift fluid to the suprachoroidal space and change choroidal perfusion. MATERIALS AND METHODS: This prospective study included 34 eyes of 17 bilateral glaucoma or ocular hypertensive patients who had no previous hypotensive therapy. Each patient had both eyes treated with latanoprost. Each patient also underwent a complete ophthalmological examination and optical coherence tomography measurement. Choroidal thickness measurements by optical coherence tomography were carried out on the first visit before latanoprost use and at time intervals of 7 and 30 days of therapy. RESULTS: The patients' mean age was 62.3±11 years (range, 30 to 83 y). Of 17 patients, 7 were female individuals. There were no significant differences in central choroidal thicknesses at the fovea, or at each point within the horizontal nasal and temporal quadrants between visits (P<0.05 for all comparisons). CONCLUSIONS: The current study showed that choroidal thickness does not change after latanoprost therapy. However, the choroidal changes of anterior part of the eye can be effected by the latanoprost therapy. Future studies investigating the anterior part of the eye and focusing on both choroidal perfusion and choroidal thickness may give additional information concerning the mechanism of action.

Management of Subfoveal Perfluorocarbon Liquid: A Review.

Perfluorocarbon liquid (PFCL) has been widely used in vitreoretinal surgeries, especially in retinal detachment treatment. A prominent complication of intraoperative PFCL application is inadvertent subretinal PFCL retention. Subfoveal PFCL, even in small amounts, receives much attention due to its potential side effect on the macular structure and function. Whether to observe with follow-up or to deal with surgery is often an intractable problem in the management of subfoveal PFCL. Safety and necessity are the 2 key issues in considering surgical treatment, that is, can we avoid surgically induced macular injury and will surgery be beneficial for the recovery of vision? Herein, the authors review sub-foveal PFCL retention with its risk factors, morphological manifestations, pathological studies, clinical natural consequences, and different surgical methods with their outcomes. Analysis of the existing literature shows that visual acuity improved significantly after subfoveal PFCL removal or displacement and was positively correlated with visual acuity before the operation.

BETTER PROGNOSIS FOR EYES WITH PRESERVED FOVEAL DEPRESSION AFTER INTRAVITREAL RANIBIZUMAB INJECTION FOR MACULAR EDEMA SECONDARY TO CENTRAL RETINAL VEIN OCCLUSION.

PURPOSE: To determine the prognosis of eyes with central retinal vein occlusion that had a preserved foveal depression at the baseline and were treated by intravitreal ranibizumab injections (IRIs). METHODS: The authors reviewed the medical records of 23 eyes of 23 consecutive treatment-naive patients who received IRIs to treat the macular edema due to central retinal vein occlusion. Eyes were classified by the pre-IRI presence or absence of a foveal depression. A foveal depression was defined as a central foveal thickness that was <50 µm thinner than the average thickness at 200 µm temporal and nasal to the central fovea. The characteristics of the two groups were compared. RESULTS: Seven of 23 eyes had a preserved foveal depression before the IRI. The mean number of injections within 12 months after the initial IRI was significantly fewer (P < 0.001) in eyes with foveal depression (1.6 ± 0.5) than in eyes without foveal depression (4.3 ± 1.3). The mean best-corrected visual acuity at 12 months after the initial IRI was significantly better (P = 0.003) in eyes with foveal depression (0.10 ± 0.17 logarithm of the minimum angle of resolution [logMAR] units; 20/25 Snellen units) than in eyes without foveal depression (0.77 ± 0.54 logMAR units; 20/118 Snellen units). CONCLUSION: These results indicate that the prognosis is better for eyes with a foveal depression before the IRI treatment for a macular edema secondary to central retinal vein occlusion.

TWENTY-FOUR MONTH FOLLOW-UP OF TOCILIZUMAB THERAPY FOR REFRACTORY UVEITIS-RELATED MACULAR EDEMA.

BACKGROUND: To report the 24-month efficacy and safety of the interleukin-6 receptor antagonist tocilizumab (TCZ) for refractory uveitis-related macular edema (ME). METHODS: Data were obtained by standardized chart review. Patients with quiescent uveitis seen at a single tertiary referral center, for whom ME was the principal cause of reduced visual acuity. OUTCOME MEASURES: Central foveal thickness measured by optical coherence tomography; degree of anterior and posterior chamber; inflammation (Standardization of Uveitis Nomenclature Working Group criteria); and visual acuity (Snellen and logarithm of the minimum angle of resolution) were recorded in all patients during TCZ therapy at months 1, 3, 6, 12, 18, and 24. RESULTS: Sixteen eyes from 12 patients (10 women) were included. Mean age was 34.6 years. Mean duration of ME was 13.2 years. All patients achieved 24 months of follow-up and that is the census date for data collection. Before TCZ was commenced, ME was present, and all patients had been previously treated with immunosuppressive therapy and biologic agents. Uveitis diagnoses were juvenile idiopathic arthritis associated, uveitis (n = 6), birdshot chorioretinopathy (n = 2), idiopathic panuveitis (n = 2), sympathetic ophthalmia (n = 1), and ankylosing spondylitis (n = 1). Mean central foveal thickness (95%; confidence interval) was 516 ± 55 µm at baseline, improving to 274 ± 13 at Month 12 (P = 0.0004), and sustained at 274 ± 14 at Month 24 of follow-up (P = 0.00039). Mean logarithm of the minimum angle of resolution best-corrected visual acuity improved from 0.78 ± 0.18 (Snellen 20/120 ± 20/30) at baseline to 0.42 ± 0.17 (20/52 ± 20/30) at Month 12 (P = 0.0001) and 0.40 ± 0.17 (20/50 ± 20/30) at Month 24 of follow-up (P = 0.0002). Tocilizumab therapy was withdrawn in 5 patients with sustained remission at Month 12 but in all, ME relapsed between 1 and 3 months after TCZ discontinuation. Rechallenge of TCZ infusions led to recovery of uveitis control and ME resolution. Two adverse events were reported during two 4-month follow-ups: one Grade 1 neutropenia and one community-acquired pneumonia. CONCLUSION: In this long-term study, TCZ was effective and had a comparable safety profile to published data for TCZ use in other indications, when used for the treatment of refractory uveitis-related ME.

FUNDUS AUTOFLUORESCENCE FINDINGS IN EARLY CHLOROQUINE MACULOPATHY.

BACKGROUND/PURPOSE: Toxic maculopathy is a rare but severe complication of chloroquine intake. Although the phenotype of established maculopathy was analyzed in detail, few data exist on the ophthalmologic findings in the early stage. METHODS: The authors present 4 female patients with unequivocal signs of chloroquine maculopathy (bilateral [peri-]central scotoma in the visual fields, structural alterations of the macula in the optical coherence tomography) but normal or atypical findings as to fundus autofluorescence imaging. RESULTS: In all patients, optical coherence tomography showed perifoveal thinning and subtle alterations of the outer retinal layers. In one patient, the latter was limited to the pericentral region, whereas it showed a more diffuse distribution in two other patients. One patient showed a combination of pericentral and diffuse damage. Multifocal electroretinography was recorded in three patients and revealed the typical (peri-)central amplitude reductions. CONCLUSION: A normal fundus autofluorescence does not rule out toxic maculopathy. Optical coherence tomography and multifocal electroretinography seem to be more sensitive in the early stage of the disease. In case of typical complaints and visual fields, the optical coherence tomography has to be evaluated for subtle alterations of the outer retina. Their presence justifies the cessation of the drug. Multifocal electroretinography may be of special value in these problematic cases.

Perifoveal interdigitation zone loss in hydroxychloroquine toxicity leads to subclinical bull's eye lesion appearance on near-infrared reflectance imaging.

PURPOSE: To characterize the ultrastructural and functional correlates of hydroxychloroquine (HCQ)-induced subclinical bull's eye lesion seen on near-infrared reflectance (NIR) imaging. METHODS: An asymptomatic 54-year-old male taking HCQ presented with paracentral ring-like scotoma, abnormal multifocal electroretinography (mfERG) and preserved ellipsoid zone on optical coherence tomography (OCT). Dense raster OCT was performed to create en face reflectivity maps of the interdigitation zone. Macular Integrity Assessment (MAIA) microperimetry and mfERG findings were compared with NIR imaging, en face OCT, retinal thickness profiles and wave-guiding cone density maps derived from flood-illumination adaptive optics (AO) retinal photography. RESULTS: The bull's eye lesion is an oval annular zone of increased reflectivity on NIR with an outer diameter of 1450 µm. This region corresponds exactly to an area of preserved interdigitation zone reflectivity in en face OCT images and of normal cone density on AO imaging. Immediately surrounding the bull's eye lesion is an annular zone (3°-12° eccentricity) of depressed retinal sensitivity on MAIA and reduced amplitude density on mfERG. Wave-guiding cone density at 2° temporal was 25,400 per mm2. This declined rapidly to 12,900 and 1200 per mm2 at 3° and 4°. CONCLUSION: Multimodal imaging illustrated pathology in the area surrounding the NIR bull's eye, characterized by reduced reflectance, wave-guiding cone density and retinal function. Further studies are required to investigate whether the bull's eye on NIR imaging and en face OCT is prominent or consistent enough for diagnostic use.