[Preconceived ideas, paradoxes, and new concepts in retinal vein occlusion]. / Idées reçues, paradoxes et nouveaux concepts en matière d'occlusion veineuse rétinienne.

Retinal vein occlusion is the second cause of vascular retinopathy after diabetic retinopathy and often leads to poor visual outcome. In a simplified form, the authors attempt to rectify a number of preconceived ideas about retinal vein occlusion and introduce new concepts in order to assist in the understanding of their mechanisms. Various paradoxes are explained, such as the presence of arterial risk factors in this venous disorder, the atypical combination of retinal ischemia and the absence of vascular non-perfusion on fluorescein angiography, the fact that macular edema is larger in the ischemic form than in the well-perfused form, the aggravating role of contraceptive hormonal therapy, the protective role of substitutive hormonal therapy, etc. The current controversies are underlined: the seasonal onset of the disease, the role of vasodilator treatment, the place of etiologic screening, and the significance of prepapillary loops. Lastly, the authors summarize important basics about treatment modalities, even if there is not yet consensus on the treatment of retinal vein occlusion.

[Underlying conditions associated with the occurrence of retinal vein occlusion]. / Circonstances de survenue des occlusions veineuses rétiniennes.

BACKGROUND: Conventional risk factors for retinal vein occlusion (RVO) are well established through large epidemiological studies, but triggering factors remain poorly known. PATIENTS AND METHODS: A prospective observational study through a questionnaire was completed between January and October 2009 by patients with RVO and controls. RESULTS: Sixty-one patients, including 42 central retinal vein occlusions (CRVO) and 19 branch vein occlusions (BRVO) as well as 118 controls were included. Of the CRVO patients, 77% discovered visual loss upon awakening in contrast to only 33% of BRVO patients. The comparison between RVO and controls showed a higher proportion in the RVO group for (in order of the highest risk): migraine headache (CRVO, 21 %; BRVO, 47 %; controls, 13 %; p=0.008), hypertension (CRVO, 52%; BRVO, 63%; controls, 37%; p=0.012), glaucoma (CRVO, 33%; BRVO, 22%; controls, 16%; p=0.034), antiplatelet or anticoagulant medication (CRVO, 42%; BRVO, 33%; controls, 26%; p=0.074), hyperlipidemia, ocular trauma, sudden deafness, or vertigo. The prevalence was similar in both groups for body mass index, history of phlebitis or peptic ulcer, smoking habits, stress, fasting, dehydration, vasodilator intake, and altitude stay. CONCLUSION: In addition to the already known risk factors, this study underlines certain underlying conditions or circumstances related to the onset of RVO, such as migraine. In CRVO, three-quarters of the patients on average discovered visual loss upon awakening, which may indicate that nocturnal events may play a significant role in the pathogenesis of the occlusion.

[SPA-2: semiology for phenotyping AMD: atrophic AMD]. / SPA-2 : sémiologie du phénotype de la dégénérescence maculaire liée à l'âge : forme atrophique.

PURPOSE: The determination of homogeneous subgroups of age-related macular degeneration (AMD) is necessary for clinical and genetic studies; therefore, the development of a simple, reproducible, and discriminating classification is essential. In this second part of our study (SPA-2), we evaluated a selected list of items for atrophic AMD based on color photographs of fundus, red-free frames, autofluorescence, fluorescein angiography, indocyanine angiography, and Spectral-Domain OCT. METHODS: Ten items for atrophy were chosen from the literature and clinical experience. Twenty eyes of 20 patients with atrophic AMD were included. For each patient, the grid was completed by five independent, experienced readers from our reading center and by an expert. The Kappa coefficient was calculated for each item. RESULTS: The greatest agreement between observers was found for the item "presence of atrophy" (Kappa=1). The worst concordance was recorded for the item "size of atrophy" (Kappa=-0.0286±0.0769 to 0.1813±0.0835). CONCLUSION: The classification of atrophic AMD is complex and currently not very consensual, hence the need for a discriminant and reproducible classification grid. The evaluation of our grid for atrophic AMD shows satisfactory agreement between observers for the majority of the items. Some modifications are proposed to make it more discriminant and reproducible.

Ranibizumab for retinal angiomatous proliferation in age-related macular degeneration.

PURPOSE: To assess the 1-year functional outcome and to evaluate the morphological changes after intravitreal injections of ranibizumab in eyes affected with retinal angiomatous proliferation (RAP) due to age-related macular degeneration (AMD). METHODS: A prospective, non-randomized, interventional study was conducted on 26 consecutive patients with newly diagnosed RAP. All eyes were treatment naive and were randomized to receive intravitreal injections of ranibizumab for a 12-month period. After the first three monthly injections, re-treatment was performed in case of best-corrected visual acuity (BCVA) loss of at least five letters associated with fluid within the macula, central macular thickness (CMT) increase of at least 100 microm, and/or persistence of fluid within the macula as evaluated by optical coherence tomography, new onset macular haemorrhages, persistence of leakage from the lesions on fluorescein angiography. RESULTS: All patients completed the 12-month follow-up: 25 of the 29 treated eyes (86.2%) were stabilized, with a loss of less than 15 letters. Nineteen eyes (65.5%) maintained or improved their BCVA, and three eyes (10.3%) gained three lines or more. Overall, mean BCVA remained stable at the 12-month follow-up (-0.07 letters; P>0.05). Mean CMT significantly decreased from 386+/-147 to 216+/-74 microm at the 12-month follow-up. No significant adverse events were observed during the study. The mean number of injections was 5.8+/-1.7 during the follow-up period. CONCLUSION: The 1-year follow-up outcomes in our series suggest that ranibizumab is an effective treatment for RAP in AMD, allowing stabilization of BCVA and reduction of CMT.

Photodynamic therapy for choroidal neovascularisation secondary to basal laminar drusen.

PURPOSE: Basal laminar drusen (BLD) is a rare retinal disorder that may be complicated with choroidal neovascularisation (CNV). Here we describe four patients treated with verteporfin photodynamic therapy (PDT) for CNV secondary to BLD. METHODS: Four consecutive patients presented with subfoveal CNV secondary to BLD. Mean visual acuity was 20/50. CNV was treated with one single PDT session. RESULTS: Exsudative features of CNV were resolved after one session for all patients. After 6 months, mean visual acuity was 20/25 and remained stable. CONCLUSION: In this series, PDT was an effective treatment for CNV secondary to BLD.

[Epidemiology of age related macular degeneration]. / Epidémiologie de la dégénérescence maculaire liée à l'âge.

Age-related macular degeneration (ARMD) is a multifactorial and polygenic disease and is the main cause of vision loss in developed countries. The environmental factors of ARMD can modify prevalence and incidence of this disease. This article is a review of the main environmental factors currently recognized as at risk or protective factor for ARMD. Modification of these factors is of crucial importance because it could delay the onset of exudative or atrophic forms of the disease.

[Retinal vein occlusion and obstructive sleep apnea syndrome]. / Occlusion veineuse rétinienne et syndrome d'apnée du sommeil.

PURPOSE: Obstructive sleep apnea syndrome (OSAS) is a very common disease and has recently been increasingly incriminated in the initiation and progression of numerous cardiovascular, neurologic, and ophthalmologic diseases. In ophthalmologic practice, it may be related to glaucoma, nonarteritic anterior ischemic optic neuropathy, visual field defects, papilledema, central serous chorioretinopathy, and floppy eyelid syndrome. Because of personal observations, we investigated its link with retinal vein occlusion (RVO). OBSERVATION: We report the observations on three patients who presented with retinal vein occlusion and who were investigated positively for OSAS, including patients with no conventional vascular risk factors. DISCUSSION: The local and systemic effects of OSAS could explain, in some patients, the occurrence and/or the aggravation of RVO. The first-stage effects of OSAS are nocturnal hypoxemia, hypercapnia, intrathoracic pressure changes, arousals, and sleep fragmentation. RVO could be a consequence of a slow-down of blood flow circulation secondary to hypoxemia and elevated nocturnal intracranial pressure. The arousals cause an additional acute increase in arterial blood pressure. Ancillary effects include increased platelet aggregability, increased sympathic activation, oxidative stress, vascular endothelial dysfunction, inflammation, and metabolic dysregulation. CONCLUSION: This short series for the first time reports RVO patients presenting with OSAS. This suggests that OSAS, by acting on retinal microcirculation, could be an additional risk factor for the occurrence or the aggravation of RVO. Further studies are needed to confirm this possible relationship.

Nutritional AMD treatment phase I (NAT-1): feasibility of oral DHA supplementation in age-related macular degeneration.

PURPOSE: To create a pilot study in order to evaluate the feasibility of a prospective case-control study of oral supplementation with fish oil (docosahexaenoic acid [DHA]; eicosapentaenoic acid [EPA]) in a population with age-related macular degeneration (AMD). METHODS: A homogeneous group of 38 patients with drusenoid pigment epithelial detachment in one eye (PED) without choroidal new vessels (CNV) was selected. A complete ophthalmologic examination, and a complete profile of fatty acids in serum (S) and in red blood cell membranes (RBCM), were recorded at day 0 and month 6. In group 1, 22 patients were orally supplemented with EPA (720 mg/day) and DHA (480 mg/day) during 6 months. In group 2, 16 patients were followed as controls. Nutritional recommendations on fish consumption were given to both groups. RESULTS: In group 1, after 6 months supplementation we observed a significant blood enrichment in EPA (EPA-S: 2.20 vs 0.79, p<0.0001 and EPA-RBCM: 2.24 vs 0.85, p<0.0001) and in DHA (DHA-S: 2.47 vs 1.56, p<0.0001 and DHA-RBCM: 6.47 vs 4.67, p<0.0001). No change was observed in group 2 despite nutritional recommendations. In this short followup, no evolution to CNV was noted in either of the two groups. Neither side effects nor dropouts were observed in either of the groups. DISCUSSION: This study supports the feasibility of a long-term double-masked prospective case-control study in an AMD population in order to evaluate a potential benefit from oral supplementation with DHA.

Infrared features of classic choroidal neovascularisation in exudative age-related macular degeneration.

AIM: Wet age-related macular degeneration (AMD) represents a heterogeneous group of phenotypes, all defined by fluorescein angiography features (FA). Imaging of wet AMD is extensively described in literature, including colour pictures, FA, indocyanine green angiography (ICG) and optical coherence tomography (OCT). The purpose of this study was to describe features of infrared (IR) pictures of a homogeneous subgroup of classic choroidal neovascularisation (CNV) associated with wet AMD, METHODS: We analysed 22 eyes of 22 consecutive patients with classic CNV. All patients underwent a complete ophthalmological examination including colour fundus photography, infrared picture, fluorescein angiography, indocyanine green angiography and an optical coherence tomography. RESULTS: Infrared pictures revealed a whitish ring surrounding the neovascular lesion in all eyes (22/22). The whitish ring corresponded in all cases to the borders of the CNV defined on the early phase of FA and ICG pictures. The ring had an "O-shape" in 15/22 cases (68%) and a "U-shape" in 7/22 cases (32%). CONCLUSION: Analysis of infrared pictures in classic CNV constantly revealed a whitish ring that is correlated to the limits of the lesion. IR picture is a non invasive imaging of the macula, but the specificity of the features needs to be investigated in further studies.

Pegaptanib sodium for occult choroidal neovascularization in neovascular age-related macular degeneration: a prospective case series.

PURPOSE: To assess the effects of pegaptanib in the treatment of subfoveal occult choroidal neovascularisation (CNV) associated with neovascular age-related macular degeneration (NV-AMD) in a compassionate use program in France. METHODS: Pegaptanib was authorized for patients with CNV-associated visual impairment and in whom usual care (thermal laser photocoagulation or photodynamic therapy with verteporfin) was not appropriate. Patients with occult CNV lesions received intravitreous pegaptanib (0.3 mg every 6 weeks) and were followed with repeated fluorescein angiography, scanning laser ophthalmoscopy-infracyanine green angiography, and ocular coherence tomography through 52 weeks. RESULTS: Of 56 patients (predominantly occult, N=22; purely occult, N=8; occult with chorioretinal anastomosis, N=12; occult with pigment epithelial detachment, N=14), 30% had earlier treatment. All received eight pegaptanib injections. At week 52, 79% were responders (lost <15 letters of visual acuity), 43% gained >or=0 letters, and 9% gained >or=15 letters. The best functional results were obtained in the predominantly and pure occult subgroups (responders, 86 and 75%; gained >or=0 letters, 50 and 50%). Maximum visual outcomes that correlated with morphologic improvements on each diagnostic imaging tool were seen after at least three injections. No significant ocular or systemic adverse events occurred. CONCLUSION: Treatment with pegaptanib was associated with objective functional improvements that can be correlated with objective clinical improvements on routine diagnostic imaging tools in patients with occult NV-AMD. Optimum treatment results appear after at least 4 months of therapy in the majority of cases.

[Intravitreous injection: retrospective study on 2028 injections and their side effects]. / Injection intravitréenne: évaluation rétrospective de la technique et des complications d'une série de 2028 injections.

OBJECTIVE: To observe the tolerance of repeated intravitreous injections over the short and long term and to analyze their complications. PATIENTS AND METHODS: The clinical records of consecutive patients having one or several intravitreous injections between 2002 and 2007 were evaluated, for all indications except the treatment of endophthalmitis. RESULTS: 2028 intravitreous injections were performed, mainly for age-related macular degeneration (n=1 192) or macular edema secondary to diabetes mellitus or retinal vein occlusion (n=41). The injected drug was triamcinolone acetonide 4 mg (339 injections), pegaptanib sodium 0.3 mg (1179 injections), and ranibizumab 0.3 (497 injections). The patients received 1-27 intravitreous injections per eye. The main complications were endophthalmitis (two after triamcinolone, 0.1% of the total group), pseudoendophthalmitis (two after triamcinolone, 0.1% of the total group), hypertony (7.69% of the total group, 13.78% after triamcinolone, 3.56% after pegaptanib, 1.21% after ranibizumab), including five cases of acute hypertony with transient light perception loss after ranibizumab, cataract (0.44% of total group), and macular hole (one patient after triamcinolone). No case of retinal detachment nor systemic complication was observed. DISCUSSION: Most of the complications were observed with the use of nonfiltered triamcinolone. The incidence of endophtalmitis was considerably lower with increased experience and the use of a dedicated room for the injections. Repeated injections were locally well tolerated. CONCLUSION: With the strict respect of asepsis rules, intravitreous injection seems well tolerated over the short and long term.

[Evolving intravitreous injection technique]. / Evolution des pratiques pour la réalisation des injections intravitréennes.

The technique of intravitreous injections has been well documented for several years. Recently, a descriptive article on the intravitreous injections procedure was published in the Journal Français d'Ophtalmologie, and the AFSSAPS (French agency for drug safety) released recommendations concerning this matter on the occasion of commercial launch of pegaptanib. Since that time, the number of intravitreal injections has considerably increased, because anti-VEGF drugs had been made available to ophthalmologists, and several teams have performed a large number of procedures, allowing them to better comprehend intravitreous injections. The present paper describes our current practice of intravitreous injections. Several specialists have exchanged their experiences and issued a common synthesis. Detailed modifications of the initial recommendations have been suggested, with such basic changes such as abandoning preoperative pupil dilatation and easing postsurgical monitoring. Follow-up examinations should be adapted to each patient rather than being systematic. The suggested modifications do not change the procedure of intravitreous injections substantially, but they simplify many steps and detail the various procedures when consensus is lacking.

[Spectral Domain OCT in age-related macular degeneration: preliminary results with Spectralis HRA-OCT]. / Tomographie par cohérence optique de type Spectral Domain dans la dégénérescence maculaire liée à l'âge. Premiers résultats avec Spectralis HRA-OCT.

PURPOSE: Optical coherence tomography (OCT) imaging has become extremely valuable in demonstrating the presence of neurosensory or retinal pigment epithelial elevation or detachment associated with occult choroidal newvessels. This imaging method has recently been improved using the Fourier Transform and is called Spectral Domain-OCT or SD-OCT. The preliminary results using this imaging technique can now be used to analyze the advantages of the technique's sensitivity and acquisition speed. MATERIAL: and methods: A consecutive series of 100 AMD patients was examined prospectively and followed with the Spectralis HRA-OCT device (Heidelberg Engineering, Heidelberg, Germany). Each patient underwent a complete ophthalmologic examination, including biomicroscopy, fluorescein and ICG angiographies, and OCT examinations. RESULTS: Different clinical forms of early AMD and advanced ARMD, either atrophic or exudative, can benefit from this new examination. The various changes were registered, mainly at the level of the outer nuclear layer, the outer limiting membrane, and the interface between the inner and outer segments. Intra- or subretinal fluid accumulation and the variations in retinal thickness were precisely analyzed and compared during follow-up using the Tomography Laser Tracking System. CONCLUSION: The Tomography Laser Tracking System can efficiently evaluate the results of treatment, correlated with the angiographic and functional data, providing great assistance in diagnosis and indications for treatment and retreatment. Quantitative measurements can be taken, not only in the lesion area, but also of their volume (especially for drusen), which may become useful in detecting complications in high-risk patients.

Correlation of visual function impairment and OCT findings in patients with Stargardt disease and fundus flavimaculatus.

PURPOSE: To investigate the relationship between morphologic lesions of the retina and functional abnormalities in patients with Stargardt disease (STGD) and fundus flavimaculatus (FFM). DESIGN. Case-controlled, prospective, comparative observational study. METHODS: A complete ophthalmologic examination, including best-corrected visual acuity (BCVA) and optical coherence tomography (OCT), was performed in 61 eyes of 32 consecutive patients with STGD/FFM and in 60 eyes of 30 matched healthy control subjects. Furthermore, fundus-related perimetry was performed in 12 of the affected eyes. RESULTS: The age ranged from 21 to 71 years in STGD/FFM patients and from 21 to 72 years in controls. BCVA ranged from 20/20 to 20/400 and from 20/20 to 20/32, respectively, in STGD/FFM patients and in controls. A foveal thinning was found by OCT Stratus in almost all cases (average 160 microm) compared with controls (average 210 microm) (p<0.001). BCVA impairment significantly correlated to the degree of foveal thinning (r2=0.16; p=0.0014). Moreover, in STGD/FFM patients the authors observed two types of hyperreflective deposits which were not correlated with BCVA impairment or foveal thinning. In addition, fundus-related perimetry revealed a stable fixation in 8/12 eyes, that was predominantly central in only 4 of these eyes. A smaller degree of foveal thinning correlated to a more stable fixation (p=0.0108), even if not predominantly central (p=0.0218). CONCLUSIONS: In this series, lower visual acuity and unstable fixation correlated with a greater transverse foveal thinning. OCT and fundus-related perimetry may be useful tools in STGD/FFM patients.

Retinal photocoagulation for proliferative sickle cell retinopathy: a prospective clinical trial with new sea fan classification.

PURPOSE: To compare the clinical outcome of stage III proliferative sickle cell retinopathy (PSR) treated by peripheral retinal scatter photocoagulation to natural course disease. METHODS: Long-term follow-up of 101 patients enrolled in a prospective trial of photocoagulation for PSR has been completed. Among 202 eyes of 101 patients enrolled at the University Eye Clinic of Créteil, 73 eyes showed a stage III PSR, which the authors further divided into five new grades (A, B, C, D, E) considering size, hemorrhage, fibrosis, and visible vessels. Grading was based on a three-mirror fundus examination, 360 degrees color photographs, and fluorescein angiography. Mean follow- up was 4 years. RESULTS: Thirty-eight treated eyes and 35 untreated eyes were included in this study. The evolution was not statistically significant between treated and untreated groups concerning flat sea fan <1 MPS disc area (grade A) or elevated sea fan with partial fibrosis (grade C). Progression and regression were compared between the two groups for grade B, resulting statistically significant (p<0.05). Nine complications (13%) were observed, which only occurred in untreated patients with elevated sea fan and hemorrhage (grade B) or complete fibrosed sea fan with well defined vessels (grade E) (p<0.05). CONCLUSIONS: These data suggest that patients with grade A or C new sea fan classification should not be initially treated but observed.

[Monitoring anti-VEGF drugs for treatment of exudative AMD]. / Injections intra-vitréennes d'anti-VEGF pour la dégénérescence maculaire liée à l'âge exsudative: place des examens complémentaires dans les décisions de retraitement.

AIM: Anti-VEGF drugs are the most recent treatments for choroidal neovascularization, the most severe complication of the age-related macular degeneration (AMD). These drugs are administered by intravitreal injections. Several clinical studies have demonstrated their advantages. However, these same studies have not established the modalities for monitoring their efficacy. The aim of this paper is to provide an in-depth look at the existing practices in monitoring anti-VEGF therapy among different French specialists. METHODS: Several meetings were held with specialists coming from both the hospital setting and private practice to share their practices in monitoring anti-VEGF therapy and to propose more rational monitoring to standardize practices. RESULTS: The physicians attached an increasing importance to optical coherence tomography (OCT) in monitoring anti-VEGF drugs after intravitreal injection. They acknowledged the value of fluorescein angiography when initiating the treatment and 3 months after beginning anti-VEGF therapy. They advise using fluorescein angiography every time that functional results are not at the level expected by the physician or the patient. The authors provide a flow chart that should help in deciding on retreatment. CONCLUSION: The authors suggest the use of a flow chart aimed to define indications of retreatment according to clinical response and OCT results.

[Comparison of macular limited translocation and photodynamic therapy for management of choroidal neovascularization in degenerative myopia: a retrospective study]. / Etude rétrospective comparant la translocation maculaire limitée et la photothérapie dynamique dans la néovascularisation choroïdienne rétrofovéale de la myopie forte.

PURPOSE: To analyze the results of limited macular translocation (MT) and photodynamic therapy (PDT) in subfoveal choroidal neovascularization due to degenerative myopia, with a minimum follow-up of 12 months. METHODS: Retrospective review of 55 consecutive patients: 31 eyes were treated using PDT and 24 were operated on with the limited macular translocation technique with chorioscleral infolding described by de Juan. Before and after each treatment, a complete examination comprised visual acuity, fundus examination, fluorescein angiography, and optical coherence tomography. Mean follow-up was 14 months in the PDT group and 19 months in the MT group. RESULTS: The improvement in visual acuity was better in the MT group than in the PDT group and was correlated with younger age (p<0.001). At month 12, visual acuity improved by 3 ETDRS lines or more in 6 six eyes of the PDT group (19%), with no improvement over 6 lines. In the MT group, visual acuity improved by 3 lines in 14 eyes (58%) including 8 eight eyes (33%) with an improvement of 6 lines or more. Final visual acuity remain unchanged (+/-2 lines) in 16 eyes of the PDT group (66%) and 8 eight eyes of the MT group (33%), and decreased in 9 nine eyes in the PDT group (29%) versus 2 two eyes in the MT group (8%). Mean gain in visual acuity at 12 months was +3.5 ETDRS lines in the MT group and -0.1 line in the PDT group (p=0.001). The mean displacement of the fovea after translocation was 950 microm. The mMean number of PDT treatments was 2.3 during the 12-month follow-up. CONCLUSIONS: Limited macular translocation allowed provided a significant improvement in visual acuity in some eyes with subfoveal neovascularization in myopia, especially in young patients, and resulted in a moderate rate of complications. Longer follow-up and further controlled and randomized studies are required to confirm these encouraging findings.

[Clinical case of management with intravitreal injection of Ranibizumab (Lucentis) on AMD predominant occult CNV: 6-month follow-up with FA, ICG-A, and OCT]. / Traitement par injection intra-vitréenne de Ranibizumab (Lucentis) pour des néovaisseaux choroïdiens occultes prédominants liés à la DMLA: étude et suivi par imagerie en fluorescéine, infracyanine et OCT pendant 6 mois.

INTRODUCTION: Controlled clinical trial results of occult choroidal neovascularization (CNV) management in age-related macular degeneration (AMD) using intravitreal injections of Ranibizumab have shown significant improvement in vision for the treated group. CASE REPORT: The first clinical case of minimally classic CNV is reported here with the results at 6 months, not only with changes in visual acuity but also with complete imaging at each follow-up with fluorescein angiography, infracyanine angiography using the scanning laser ophthalmoscope (SLO) and with OCT examination. After the second injection, the patient experienced improvement in vision and complete regression of all symptoms to date (5 months after the first injection), showing very favorable progression during the entire follow-up. CONCLUSION: This clinical case shows extremely favorable progression of the minimally classic lesion resulting from the first two injections of Lucentis. The situation is now stabilized in terms of function and morphology, as shown by the fluorescein and infracyanine SLO angiography and OCT examination.