Ultra-high resolution optical coherence tomography analysis of bull ’ s eye maculopathy in chloroquine users

Purpose: Register and compare anatomical changes, structural and quantitative found in optical coherence tomography Stratus and Topcon 3D in chronic users of chloroquine. Methods: Five patients were diagnosed with toxic “bull’s eye” maculopathy was submitted to macular optical coherence tomography examination (Stratus and Topcon 3D). Results: Both tools demonstrated an increase reflectivity of choriocapillaris unit just foveal retinal pigment epithelium atrophy. However, Topcon 3D provided to all patients better description of the line corresponding to the transition between inner and outer segments of photoreceptors. Using the possibility of assembling threedimensional images and subtraction selective retinal layers, we found a lesion with a target that reflects the greater thickness of retinal pigment epithelium in central and parafoveal region that is matched to preserve macular photoreceptors.Conclusion: it was observed better resolution and faster image capture by Topcon 3D than Stratus OCT, that provided more detailed analysis of the line corresponding to transition between outer and inner segment of photoreceptors in macular region. With Topcon 3D, it was possible to evaluate soundly the thickness of retinal pigment epithelium in central and parafoveal region that caused an increase reflectivity of choriocapillaris creating a image with a target unpublished before.


C
hloroquine is an antimalarial drug, prescribed for treatment of amebiasis, systemic lupus eythematous, rheumatoid arthritis and for prophylaxis of malaria.Retinal toxicity with degeneration of neurosensory retina and of retinal pigment epithelium (RPE) as a result of long-term daily use of chloroquine has been well described (1)(2)(3)(4)(5) .Most of cases of retinal toxicity have developed when higher than currently recommended dose (3,5 mg/Kg/day using lean body weight) was used (6) .
Paracentral scotoma may be the earliest manifestation of retinal toxicity and may precede the development of any ophthalmoscopic or ERG abnormality (7) .Loss of the foveal light reflex and subtle macular pigment stippling may appear before the development of the classic bull's eye maculopathy, in which a ring of depigmentation surrounded by an area of hyperpigmentation is seen centered on the fovea.Visual acuity decreases when the RPE abnormalities involve the center of the macula.In more severe cases, chloroquine retinopathy develops into the appearance of primary retinal degeneration with narrowed retinal vessels, optic disc pallor and severe visual acuity loss (1)(2)(3)(4)(5) .
In the last few years, the optical coherence tomography (OCT) has been used as non-invasive tool to access the macular anatomical status in many macular diseases (8) .Spectral domain OCT (SD OCT) enhances the visualization of intraretinal architectural morphology relative to time domain OCT in many retinal diseases including cases of retinal toxicity (9)(10)(11)(12)(13) .SD OCT also provides 50-70 times faster data acquisition that enables visualization in entire cubes that can be viewed in three dimensions and also gives a single-layer surface maps of RPE.SD OCT images with 5 microns of transverse resolution also enables better visualization of the inner segment and outer segment (IS/OS) photoreceptor (PR) junction and RPE, leading to a different understanding of pathogenic mechanisms for retinal diseases (10)(11)(12) .

METHODS
From february 2008 to march 2009, 234 patients, chronic users of chloroquine, were referred to ophthalmologic examination.Of these, five were diagnosed with toxic "bull's eye" maculopathy.This diagnosis was based on historical chronic use of chloroquine, angiographic and fundus findings.These patients also underwent measurement of visual acuity logMAR in best corrected (on the scale of the Early Treatment Diabetic Retinopathy Study -ETDRS) and macular OCT (Stratus OCT and Topcon 3D OCT).It was considered both eyes of each patient for analysis statistics, except in a patient with macular edema after cataract surgery in one eye.To obtain the images with Stratus OCT version 4.0 (Carl Zeiss Meditec) scans were used Linear 5mm through the fovea in the vertical and horizontal fast retinal map.In Topcon 3D OCT, scans were performed in program linear (cross hair) and maps retinal (retinal map).We compared anatomical changes, structural and quantitative found in OCT Stratus and Topcon 3D.Using these parameters in Topcon 3D OCT, were analyzed three-dimensional maps of the surface of RPE.The Ethics Committee approved the study.

RESULTS
Demographic data of 5 patients are shown in table 1. Qualitative analysis of images obtained with both devices showed absence of changes in the vitreous-retinal interface in all patients.Foveal depression is present but with angled edges more acute in relation RPE line.Evaluation of neurosensory retina is hampered by a marked decrease in this layer fovea.Both tools demonstrated an increase reflectivity of choriocapillaris by absence of blocking light in caused by just foveal RPE atrophy.However, Topcon 3D OCT provided to all patients better description of the line corresponding to the transition between inner and outer segments of photoreceptors.Both machines devices enabled to detected reduction of macular thickness and volume in 9 eyes examined.Using tridimensional analysis, when part of the neu-  rosensory retina is subtracted (internal limiting membrane to outer limiting membrane), were observed a novel target in an image where the central and paracentral rings show a complex RPE-PR apparently more thinning (figures 1-3).

DISCUSSION
Optical coherence tomography has revolutionized the diagnosis and treatment of retinal diseases in last years.Macular thickness decrease using OCT in bull's eye maculopathy of chloroquine users has been documented in previous studies (13) , and was confirmed by both the devices used in this study.In this paper, the better resolution and faster image capture by SD OCT provided more detailed analysis of the line corresponding to transition between outer and inner segment of photoreceptors in macular region.Because of the possibility of assembling threedimensional images and subtraction selective retinal layers, we found an unpublished document, a lesion with a target that reflects the greater thickness of RPE in central and parafoveal region that is matched to preserve macular photoreceptors.
It was possible to correlate the areas where the target pattern is less evident with thinning of the neurosensory retina in same location, which may indicate that the pattern observed in RPE target will be the "paid" with disease's progression.Thus, in near future, a comparative analysis of three-dimensional graphics of RPE may enable the analysis of progression of maculopathy in bull's eye induced by chloroquine.

Figure 3 :
Figure 3: Analyzed three-dimensional map of the surface of RPE with central and paracentral rings show a complex RPE-PR more thinning

Figure 1 :
Figure 1: Stratus OCT linear scan with just foveal RPE atrophy Figure 2: Topcon 3D OCT linear scan with just foveal RPE atrophy with the line corresponding to the transition between inner and outer segments of photoreceptors