Clinical Characteristics and Risk Factors of Extensive Macular Atrophy with Pseudodrusen: The EMAP Case-Control National Clinical Trial.

PURPOSE: To assess the association of clinical and biological factors with extensive macular atrophy with pseudodrusen (EMAP) characterized by bilateral macular atrophy occurring in patients aged 50 to 60 years and a rapid progression to legal blindness within 5 to 10 years. DESIGN: A national matched case-control study. PARTICIPANTS: Participants were recruited in 10 French Departments of Ophthalmology and their associated clinical investigation centers. All 115 patients with EMAP had symptoms before the age of 55 years due to bilateral extensive macular atrophy with a larger vertical axis and diffuse pseudodrusen. Three controls without age-related macular degeneration (AMD) or retinal disease at fundus examination were matched for each patient with EMAP by gender, age, and geographic area (in total 415). METHODS: Subjects and controls underwent an eye examination including color, red-free autofluorescent fundus photographs and spectral-domain optical coherence tomography with macular analysis. The interviews collected demographic, lifestyle, family and personal medical history, medications, and biological data. Associations of risk factors were estimated using conditional logistic regression. MAIN OUTCOME MEASURES: Extensive macular atrophy with pseudodrusen status (cases vs. controls). RESULTS: Extensive macular atrophy with pseudodrusen most frequently affected women (70 women, 45 men). After multivariate adjustment, family history of glaucoma or AMD was strongly associated with EMAP (odds ratio [OR], 2.3, P = 0.008 and OR, 1.5, P = 0.01, respectively). No association was found with cardiac diseases or their risk factors. Mild and moderate kidney disease and higher neutrophil rate were associated with a reduced risk of EMAP (OR, 0.58, P = 0.04; OR, 0.34, P = 0.01; and OR, 0.59, P = 0.003, respectively). On the contrary, eosinophilia (OR, 1.6; P = 0.0002), lymphocytosis (OR, 1.84; P = 0.0002), increased erythrocyte sedimentation rate (OR, 6.5; P = 0.0005), decreased CH50 (P = 0.001), and high plasma C3 level (P = 0.023) were significantly associated with a higher risk of EMAP. CONCLUSIONS: This study documents an association between EMAP and family history of AMD and glaucoma, a clear female predominance, and a systemic inflammatory profile. The reduced CH50 and increased C3 plasma values could reflect a more severe complement pathway dysfunction than in AMD, leading to early pseudodrusen and rapid development of geographic atrophy. There is no association of EMAP with AMD cardiac diseases or cardiac risks, including cigarette smoking.

Intravitreal dexamethasone 0.7-mg implant for radiation macular edema after proton beam therapy for choroidal melanoma.

PURPOSE: To evaluate the efficacy of dexamethasone 0.7-mg intravitreal implant in patients with radiation macular edema after proton beam therapy for choroidal melanoma. METHODS: Five patients' charts were retrospectively reviewed. The main outcome measures were visual acuity and mean central retinal thickness. RESULTS: All patients received a radiation dose of 60 cobalt gray equivalent. Radiation macular edema occurred within a mean time of 26 months after irradiation. Mean preinjection visual acuity was 41 Early Treatment Diabetic Retinopathy Study letters. Mean central retinal thickness was 487.1 µm. Two months after injection, mean visual acuity was 47 Early Treatment Diabetic Retinopathy Study letters. It improved for 3 patients (+4, +9 and, +15 letters) and remained unchanged for 2. Mean central retinal thickness was 331 µm. It decreased for 4 patients (-111, -134, -336, and -187 µm). Two patients underwent a second injection of dexamethasone performed 5 months after the first injection. The gain of visual acuity was +8 and +23 letters with a decrease in central retinal thickness of 158 and 262 µm, respectively. Intraocular pressure increased for 1 patient over a mean follow-up period of 6.4 months. CONCLUSION: Intravitreal dexamethasone implant can improve visual acuity in radiation macular edema. The observed beneficial effect lasted up to 5 months.

Acute macular neuroretinopathy: contribution of spectral-domain optical coherence tomography and multifocal ERG.

BACKGROUND: Acute macular neuroretinopathy is a rare disease which occurs in young women and causes sudden paracentral scotoma and typical reddish-brown macular lesions. MATERIAL AND METHODS: We report two cases of young women suffering from acute macular neuroretinopathy which we observed with spectral-domain Spectralis HRA-OCT and multifocal ERG at 3 and 7 months. RESULTS: Imaging revealed an early hyper-reflectivity of the photoreceptor layer, which changed into hyporeflectivity in the first week and remained the same in the following months, whereas visual field improved. CONCLUSIONS: Our findings show involvement primarly of the outer retina, and confirm OCT and mf ERG as important tools for diagnosis and follow-up of pathologic changes in AMNR, as other diagnostic tests often remain normal.

Retinal fluorescein and indocyanine green angiography and spectral-domain optical coherence tomography findings in acute retinal pigment epitheliitis.

PURPOSE: To determine the specific location of the initial lesion in acute retinal pigment epitheliitis. METHODS: Four patients diagnosed with acute retinal pigment epitheliitis were studied. Fundus photographs, fluorescein angiography and indocyanine green angiography, and spectral-domain optical coherence tomography findings were reviewed. RESULTS: Four healthy young patients presented with acute onset of unilateral decreased vision. Ophthalmoscopy showed macular pigment mottling with surrounding yellow hypopigmented areas at the level of the retinal pigment epithelium (RPE). Fluorescein angiography revealed transmission hyperfluorescence. Early-phase and midphase indocyanine green angiography images showed a patchy macular hyperfluorescence. At late phase of indocyanine green angiography, a hyperfluorescent halo with a cockadelike appearance of the macular area was observed. Spectral-domain optical coherence tomography showed a disruption of the photoreceptors' inner segment and outer segment interface associated with a wider disruption of the RPE inner band. These disrupted lines were replaced by a dome-shaped highly reflective lesion involving the RPE inner layer, the photoreceptors' inner segment and outer segment layers, and, in two cases, the outer nuclear layer. With time, indocyanine green angiography showed resolution of the observed lesions. Spectral-domain optical coherence tomography showed restored and continuous inner segment and outer segment layers and RPE inner band. CONCLUSION: Spectral-domain optical coherence tomography findings suggest that the initial lesion in acute retinal pigment epitheliitis is located at the junction between the photoreceptor outer segments and the apical side of the RPE cells. Indocyanine green angiography and spectral-domain optical coherence tomography show that the RPE appears to be more widely involved than the neurosensory retina.

Extraocular muscle involvement in marginal zone B-cell lymphomas of the orbit.

INTRODUCTION: Marginal zone B-cell lymphoma is the most frequent ocular adnexal lymphoma. It may involve the conjunctiva, lacrimal gland, eyelid, extraocular muscle, and orbital connective tissue. Extraocular muscle infiltration is rare. METHODS: We report here a series of 5 patients presenting with extraocular muscle infiltration due to marginal zone B-cell lymphoma, extracted from a retrospective study of 39 patients with primitive ocular adnexal marginal zone B-cell lymphoma presenting within a 15-year period, from 1993 to 2007, at two university hospitals. RESULTS: Out of 39 patients, two females and three males presented with extraocular muscle involvement (one levator muscle, one medial rectus muscle, one lateral rectus muscle, one inferior rectus muscle, and one inferior oblique muscle). In 4 cases, the right eye was involved. The median age of presentation was 60 years. Proptosis and diplopia were the main clinical signs. A mean duration of symptoms was 12 months before diagnosis was given. Three patients were stage IE at the diagnosis, according to Ann Arbor classification, and one was at stage IV. Three patients received radiotherapy and two received chemotherapy. Three patients underwent local relapses at a median time of 40 months. The patients with relapses were treated with chemotherapy alone in one case, radiotherapy alone in one case, and immunotherapy and chemotherapy in one case. The mean follow-up period was 54 months. DISCUSSION: When compared to other locations of marginal zone B-cell lymphomas of the orbit, extraocular involvement occurred in younger patients and had similar prognosis. CONCLUSION: Extraocular muscle involvement is a rare location of marginal zone B-cell lymphoma that had to be known and can simulate thyroid orbitopathy.

Changes in Ocular Subfoveal Choroidal Thickness After Carotid Endarterectomy Using Enhanced Depth Imaging Optical Coherence Tomography: A Pilot Study.

The influence of both severe chronic carotid stenosis and carotid endarterectomy (CEA) on ocular tissue has been poorly evaluated. The goal of this study was to measure subfoveal choroidal thickness (SFCT), before and after CEA, in patients with severe carotid stenosis. Consecutive patients (n = 36) with severe carotid stenosis were prospectively included. Patients (n = 19) were followed up at 1 and 3 months after CEA. The SFCT was measured bilaterally using enhanced depth imaging optical coherence tomography (EDI-OCT). Preoperatively, the median SFCT of the ipsilateral eye did not differ significantly from the contralateral eye (223 vs 236 µm; P = .75). In the ipsilateral eye, the mean SFCT was significantly higher at 1 month postsurgery and the effect was maintained at 3 months (226.3 ± 17.1 at 3 months vs 210.8 ± 16.5 µm at baseline; P < .001). For the contralateral eye, the increase in SFCT reached statistical significance at 3 months (220.1 ± 11.3 at 3 months vs 214.8 ± 11.5 µm at baseline; P = .04). The mean SFCT significantly increased bilaterally after CEA, with a more noticeable effect in the ipsilateral eye. Further studies are required to determine whether EDI-OCT could be useful as a potential marker of ophthalmologic outcomes.

Dietary, environmental, and genetic risk factors of Extensive Macular Atrophy with Pseudodrusen, a severe bilateral macular atrophy of middle-aged patients.

EMAP (Extensive Macular Atrophy with Pseudodrusen) is a maculopathy we recently described that shares pseudodrusen and geographic atrophy with Age-related Macular Disease (AMD). EMAP differs from AMD by an earlier age of onset (50-55 years) and a characteristic natural history comprising a night blindness followed by a severe visual loss. In a prospective case-control study, ten referral centers included 115 EMAP (70 women, 45 men) patients and 345 matched controls to appraise dietary, environmental, and genetic risk factors. The incidence of EMAP (mean 2.95/1.106) was lower in Provence-Côte d'Azur with a Mediterranean diet (1.9/1.106), and higher in regions with intensive farming or industrialized activities (5 to 20/1.106). EMAP patients reported toxic exposure during professional activities (OR 2.29). The frequencies of common AMD complement factor risk alleles were comparable in EMAP. By contrast, only one EMAP patient had a rare AMD variant. This study suggests that EMAP could be a neurodegenerative disorder caused by lifelong toxic exposure and that it is associated with a chronic inflammation and abnormal complement pathway regulation. This leads to diffuse subretinal deposits with rod dysfunction and cone apoptosis around the age of 50 with characteristic extensive macular atrophy and paving stones in the far peripheral retina.

Automatic three-dimensional model for protontherapy of the eye: preliminary results.

Recently, radiotherapy possibilities have been dramatically increased by software and hardware developments. Improvements in medical imaging devices have increased the importance of three-dimensional (3D) images as the complete examination of these data by a physician is not possible. Computer techniques are needed to present only the pertinent information for clinical applications. We describe a technique for an automatic 3D reconstruction of the eye and CT scan merging with fundus photographs (retinography). The final result is a "virtual eye" to guide ocular tumor protontherapy. First, we make specific software to automatically detect the position of the eyeball, the optical nerve, and the lens in the CT scan. We obtain a 3D eye reconstruction using this automatic method. Second, we describe the retinography and demonstrate the projection of this modality. Then we combine retinography with a reconstructed eye, using a CT scan to get a virtual eye. The result is a computer 3D scene rendering a virtual eye into a skull reconstruction. The virtual eye can be useful for the simulation, the planning, and the control of ocular tumor protontherapy. It can be adapted to treatment planning to automatically detect eye and organs at risk position. It should be highlighted that all the image processing is fully automatic to allow the reproduction of results, this is a useful property to conduct a consistent clinical validation. The automatic localization of the organ at risk in a CT scan or an MRI by automatic software could be of great interest for radiotherapy in the future for comparison of one patient at different times, the comparison of different treatments centers, the possibility of pooling results of different treatments centers, the automatic generation of doses-volumes histograms, the comparison between different treatment planning for the same patient and the comparison between different patients at the same time. It will also be less time consuming.

[Scar tissues of the posterior segment of the eye: histological and etiological features]. / Les membranes prolifératives et cicatricielles du segment postérieur de l'oeil. Caractéristiques histologiques et étiologiques.

Proliferative membranes of the posterior segment of the eye correspond to the formation of scar tissue in the periretinal area which arise in various pathological conditions. These membranes result from the migration of retinal and choroidal cells beyond their anatomic focus inducing the production of mutilating fibrous tissue. They are a major cause of blindness in children and adults. The development of surgical procedures reaching the posterior segment, has enabled excision of these tissues. In this review, we describe the different histological features of these membranes as well as the different etiological factors inducing their development. We propose a clinicopathological classification of these membranes.

Measurement of subfoveal choroidal thickness after cataract surgery in enhanced depth imaging optical coherence tomography.

PURPOSE: To compare subfoveal choroidal thickness (SFCT) before and after uneventful cataract surgery using enhanced depth imaging optical coherence tomography (EDI-OCT). METHODS: A prospective study was conducted on 115 eyes of 95 patients who had phacoemulsification. Measurements of SFCT were performed preoperatively, 1 day (D1), 7 days (D7), 1 month (M1), and 3 months (M3) after surgery using the EDI-OCT technique. Central retinal thickness (CRT) was measured before surgery and at M1 and M3. RESULTS: The 95 patients had a mean age of 76 ± 8.3 years. The mean SFCT at baseline was 224 ± 75 µm. It showed a negative correlation with age and axial length (P = 0.03). The SFCT significantly increased after surgery with a mean value of 232 ± 76 µm at D1 (P < 0.001), 237 ± 78 µm at M1 (P < 0.001), and 232 ± 76 µm at M3 (P < 0.001). The mean CRT increased from 234 ± 48 µm at baseline to 248 ± 48 µm at M1 (P = 0.005), and 252 ± 81 µm at M3 (P = 0.001). Three (2.6%) patients developed a pseudophakic cystoid macular edema (PCME). The greatest progression of SFCT after phacoemulsification was observed for these patients. It preceded the occurrence of pseudophakic cystoid macular edema (PCME) by 1 month. CONCLUSIONS: Mean SFCT increased after cataract surgery. The changes in baseline SFCT were greater in PCME patients and preceded the increase in CRT.

Local recurrence after uveal melanoma proton beam therapy: recurrence types and prognostic consequences.

PURPOSE: To study the prognosis of the different types of uveal melanoma recurrences treated by proton beam therapy (PBT). METHODS AND MATERIALS: This retrospective study analyzed 61 cases of uveal melanoma local recurrences on a total of 1102 patients treated by PBT between June 1991 and December 2010. Survival rates have been determined by using Kaplan-Meier curves. Prognostic factors have been evaluated by using log-rank test or Cox model. RESULTS: Our local recurrence rate was 6.1% at 5 years. These recurrences were divided into 25 patients with marginal recurrences, 18 global recurrences, 12 distant recurrences, and 6 extrascleral extensions. Five factors have been identified as statistically significant risk factors of local recurrence in the univariate analysis: large tumoral diameter, small tumoral volume, low ratio of tumoral volume over eyeball volume, iris root involvement, and safety margin inferior to 1 mm. In the local recurrence-free population, the overall survival rate was 68.7% at 10 years and the specific survival rate was 83.6% at 10 years. In the local recurrence population, the overall survival rate was 43.1% at 10 years and the specific survival rate was 55% at 10 years. The multivariate analysis of death risk factors has shown a better prognosis for marginal recurrences. CONCLUSION: Survival rate of marginal recurrences is superior to that of the other recurrences. The type of recurrence is a clinical prognostic value to take into account. The influence of local recurrence retreatment by proton beam therapy should be evaluated by novel studies.

New aspects of viral necrotizing retinitis in subacute sclerosing panencephalitis with spectral-domain optical coherence tomography.

PURPOSE: To report the clinical, angiographic, and tomographic features of an adult patient with bilateral occlusive vasculitis and necrotizing retinitis preceding the onset of subacute sclerosing panencephalitis by 3 years. METHODS: Observational case report. RESULTS: A 39-year-old white man presented with sudden onset of decreased vision in his left eye. The patient reported a history of right visual loss 3 years ago after an episode of retinal vasculitis of unknown origin. At presentation, left fundus examination showed sensory retinal detachment and retinal hemorrhages in the left macula. Fluorescein angiography revealed occlusive vasculitis. Two weeks later, several circumscribed lesions of necrotizing retinitis appeared in the macula and in the midperiphery after a centrifugal linear pattern from the optic nerve. Spectral-domain optical coherence tomography demonstrated focal areas of moth-eaten disorganization of the ganglion cell and nuclear layers with a spreading from the inner layers to the outer layers. CONCLUSION: This unusual case of adult-onset subacute sclerosing panencephalitis may help improve our knowledge regarding the mechanism of retinal involvement in this disease. Clinical and tomographic findings suggest a continuous transneuronal spread of the measles virus from ganglion cells to the photoreceptor cells.

Proton beam radiotherapy for uveal melanomas at nice teaching hospital: 16 years' experience.

PURPOSE: To present the results of uveal melanomas treated at Nice Teaching Hospital. METHODS AND MATERIALS: This retrospective study included 886 consecutive patients referred to our clinic for the treatment of uveal melanomas by proton beam radiotherapy from June 1991 to December 2007. Survival rates were determined by using Kaplan-Meier estimates, and prognostic factors were evaluated using the log-rank test or Cox model. RESULTS: The number (percent total) of subjects staged according to the TNM classification system (6th edition) of malignant tumors included 39 stage T1 (4.4%), 420 stage T2 (47.40%), 409 stage T3 (46.16%), and 18 stage T4 (2.03%) patients. The median follow-up was 63.7 months. The Kaplan-Meier overall survival rate at 5 years according to the sixth edition TNM classification was 92% for T1, 89% for T2, 67% for T3, and 62% for T4; and at 10 years, 86% for T1, 78% for T2, 43% for T3, and 41% for T4. Five factors were found to be associated with an increased death rate: advanced age, tumor thickness, largest tumor basal diameter, tumor volume, and tumor volume-to-eyeball volume ratio. The metastasis-free survival rates were 88.3 % at 5 years and 76.4 % at 10 years. The local control rates were 93.9% at 5 years and 92.1% at 10 years. The ocular conservation rates were 91.1% at 5 years and 87.3% at 10 years. CONCLUSIONS: We report the results of a large series of patients treated for uveal melanomas with a very long follow-up. Despite the large tumor volume treated, our results were similar to previously published findings relating to proton beam therapy.