Cost-effectiveness sequential modeling of ranibizumab versus usual care in age-related macular degeneration.

AIMS: To assess effectiveness, cost, and cost-effectiveness of ranibizumab versus the current medical practices of treating age-related macular degeneration in France. METHODS: A simulation decision framework over 1 year compared ranibizumab versus the usual care using two effectiveness criteria: the "visual acuity improvement rate" (greater than 15 letters on the ETDRS scale) and the "rate of legal blindness avoided". Two decision trees included various sequences of current treatments, with or without ranibizumab. RESULTS: Ranibizumab appeared significantly more effective than the usual care (p < 0.001), providing greater treatment success rate of visual acuity improvement (48.8% versus 33.9%). The cost of the ranibizumab strategy was higher (9,123 euros over 1 year for ranibizumab versus 7,604 euros for the usual care) but the average cost-effectiveness was lower--18,721 euros/success for ranibizumab versus 22,543 euros/success for usual care (p < 0.001). Considering the "legal blindness avoided" success criterion, the ranibizumab strategy appeared significantly more effective (p < 0.001), providing greater treatment success rate for of legal blindness avoided than usual care (99.7% versus 93.1%) although it was more expensive (9,196 euros over 1 year for ranibizumab versus 5,713 euros for the usual care). CONCLUSION: Ranibizumab significantly improved the rate of visual acuity improvement and reduced the rate of legal blindness. Ranibizumab appeared significantly more cost-effective than the usual treatments in terms of visual acuity improvement.

Types of choroidal neovascularisation in newly diagnosed exudative age-related macular degeneration.

AIM: To describe the types and location of choroidal neovascularisation (CNV) in exudative age-related macular degeneration (AMD), including vascularised pigment epithelial detatchments (PED), and most recently described subtypes, such as retinal choroidal anasmostosis, also termed "retinal angiomatous proliferation" (RAP). METHODS: Prospective multicentre consecutive descriptive case series. A total of 207 consecutive cases of newly diagnosed exudative AMD undergoing fluorescein angiography (FA) were recruited by 7 French referral hospital-based or private centres. Indocyanine green angiography (ICG) also was performed, when judged necessary by investigators. Types and location of CNV were classified by two independent experts and adjudicated by a third when discordant. RESULTS: All patients had FA, while ICG was performed in 50% of subjects. A total of 17.6% had classic CNV only, 5.4% and 8.3% had predominantly and minimally classic CNV, respectively. Occult CNV could be classified in occult CNV without PED (32.7%) and occult CNV with PED, ie, vascularised PED (23.9%). RAP was observed in 15.1% of cases, and accounted for 30% of vascularised PED. In 5.8% of the cases there was haemorrhagic AMD and 4.8% had fibrovascular scars. Lesions were mainly subfoveal (80%). Agreement between the centre's ophthalmologist and the final validated expert classification was moderate (kappa = 0.52 for location and 0.59 for type of lesion). CONCLUSION: This study confirms that newly diagnosed cases of exudative AMD are mainly occult and subfoveal. RAP appeared as a common lesion in patients with newly diagnosed exudative AMD.

Prevalence of reticular pseudodrusen in age-related macular degeneration with newly diagnosed choroidal neovascularisation.

AIM: To investigate the prevalence of reticular pseudodrusen (RPD) in eyes of patients presenting with newly diagnosed choroidal neovascularisation (CNV) in age-related macular degeneration (AMD), and to analyse the association between RPD, age-related maculopathy (ARM) and AMD. METHOD: Two observational consecutive prospective series. In series 1, patients with AMD with newly diagnosed CNV were sampled to determine the incidence of RPD. Eyes with and without RPD were compared by the Mann-Whitney non-parametric test and Fisher's exact test for age, sex of patients, the eye involved and type of CNV. Series 2 comprised 100 patients referred for fundus photography, fluorescein and/or indocyanine green angiography, for whom pictures showed RPD. This second cohort was then selected from a larger group of patients. RESULTS: Patients with newly diagnosed CNV in series 1 comprised 67 women and 33 men, aged 57-96 years (mean 79.5). CNV was "classic" (32 eyes), "occult" (41) or exhibited vascularised pigment epithelial detachment (PED, 11), retinal angiomatous proliferation (RAP) with or without PED (13), or haemorrhagic or fibrovascular scarring (3). In all, 24 (24%) eyes had RPD. The prevalence of RAP was significantly higher in eyes with RPD than in those without (p = 0.0128), despite the small number of patients with RAP. In series 2, 100 patients with RPD were enrolled in 3 months, and corresponded to 8% of the overall cases referred to our centre (Centre Ophtalmologique d'Imagerie et de Laser, Paris, France). There were 77 women and 23 men, aged 54-93 years (mean 79.2). Eyes with RPD (n = 155) usually exhibited signs of ARM or AMD, including soft drusen (101 eyes) and/or retinal pigment epithelium abnormalities (70), geographical atrophy (27) and/or CNV (61). In both studies, examination of blue-light fundus pictures was extremely helpful in diagnosing RPD. CONCLUSION: RPD have a high prevalence among patients with AMD with newly diagnosed CNV (24% of cases). RPD were commonly associated with ARM or AMD. This study suggests that eyes with RPD could be classified as a phenotype of ARM.

[Photodynamic therapy follow-up: when to retreat, when to observe, or when to propose an alternative treatment?]. / Thérapie photodynamique et DMLA: arguments pratiques sur la base de cas cliniques pour retraiter ou surveiller lors du suivi.

Clinical and angiographic progression after photodynamic therapy (PDT) is usually slow, sometimes fluctuating and therefore difficult to evaluate. After several sessions of PDT, angiographic follow-up remains the basis for therapeutic management involving either a new PDT session or an alternative treatment. It remains difficult, however, to evaluate the activity and progression potential of the remaining neovessels. Imaging (angiography, optical coherence tomography) and functional data both contribute to the therapeutic decision. Certain patients require several sessions for a progressive reduction of the exudation. For others, the persistence of metamorphopsias and accentuation of the scotoma despite the treatment may entail alternative treatment. Thus, a perifoveal photocoagulation can be proposed to limit the extension of the scotoma if after a reasonable number of sessions, central visual acuity is not recovered; direct photocoagulation of a persistent active neovascular contingent, distant from the fixation zone (foveal or exenterated) can be proposed if it remains on the border of a stabilized lesion; the treatment of a feeder vessel can be proposed if it becomes visible and is associated with active neovessels with a persistent central serous detachment of the neuroretina. Lastly, performance status and patient wishes are important elements in the overall therapeutic project, especially if the eye involved is the second eye, in view of quickly initiating low-vision rehabilitation.

Visual hallucinations and Charles Bonnet syndrome after photodynamic therapy for age related macular degeneration.

AIMS: To report on visual hallucinations and Charles Bonnet syndrome (CBS) that may occur in patients with age related macular degeneration (AMD) treated by photodynamic therapy (PDT) with verteporfin for choroidal neovascularisation (CNV). METHODS: 100 consecutive patients were asked to respond to an orally administered questionnaire on visual hallucinations following PDT. Three groups of patients, respectively without visual hallucinations, with unstructured visual hallucinations, and with structured hallucinations-that is, CBS, were compared by ANOVA, Scheffe's test, or the chi(2) test, to establish whether age, sex, or visual acuity, as scored on ETDRS charts, are risk factors for the occurrence of visual hallucinations. RESULTS: Five patients (5%) described transient structured visual hallucinations, including known or unknown faces and geometric patterns. Fifteen patients (15%) reported photopsias and flashing lights of various colours. These symptoms usually occurred a few days after PDT. There was no significant difference between the group of patients with structured visual hallucinations and the two other groups, with regard to age (p =0.435), sex (p =0.406), or visual acuity (p =0.835). CONCLUSIONS: Visual hallucinations and CBS appear to be a possible, although unrecognised, side effect of PDT for CNV, which occur just after treatment. These results suggest the need to include the possibility of visual hallucinations in the information given to patients before PDT.

Evaluation of a new non-mydriatic digital camera for detection of diabetic retinopathy.

AIMS: To compare the results of fundus photography using a new non-mydriatic digital camera with the results of reference standard of Early Treatment Diabetic Retinopathy Study (ETDRS) retinal photographs, for the detection of diabetic retinopathy (DR). METHODS: Fundus colour photographs were taken with a Topcon non-mydriatic camera of 147 eyes of 74 diabetic patients, without pupillary dilation (five overlapping fields of 45 degrees; posterior pole, nasal, temporal, superior and inferior). Three retinal specialists classified the photographs in a masked fashion, as showing no DR or mild non-proliferative DR (NPDR) not requiring referral, moderate or more severe NPDR and/or macular oedema, or as non-gradable image requiring referral. ETDRS 35-mm colour slides served as reference images for DR detection. RESULTS: For moderately severe to severe DR, the sensitivities of detection reported by the three observers were 92, 100 and 92%, respectively, and the specificities, 87, 85, and 88%. For four levels of DR severity (none or mild NPDR, moderate NPDR, severe NPDR and proliferative DR), the percentages of exact agreement between the three observers on the retinopathy grades assigned to the non-mydriatic photographs and to the ETDRS reference slides were 94.6, 93 and 87.6%, respectively (kappa 0.60-0.80). Sixteen eyes of nine patients (11%) were judged ungradable by at least one observer. In a second series of 110 patients, evaluated in the setting of a screening procedure, fewer photographs were ungradable (< 6%). CONCLUSION: These results suggest that fundus photographs taken by the Topcon TRC-NW6S non-mydriatic camera, without pupillary dilation, are suitable for DR screening.

Visual hallucinations immediately after macular photocoagulation.

PURPOSE: To evaluate the incidence of visual hallucinations after macular photocoagulation for choroidal neovascularization. METHODS: After macular photocoagulation for choroidal neovascularization, 60 consecutive patients were asked to respond to an orally administered questionnaire. RESULTS: Twenty-seven patients (45%) described photopsias, flashing lights of various colors. Ten additional patients (16.6%) also described structured hallucinations, including known or unknown faces, flowers, and geometric patterns, which occurred hours or a few days after photocoagulation. Patients with structured hallucinations were older (P =.04) and more often had subfoveal choroidal neovascularization (P =.005) and severe macular disease in both eyes or at least in the treated eye (P =.01). CONCLUSIONS: Visual hallucinations appear to be a frequent, albeit unrecognized, side effect of macular photocoagulation of choroidal neovascularization. The provision of proper information to patients may avoid concern about a psychiatric origin of their hallucinations.

Indocyanine green angiography in birdshot chorioretinopathy.

OBJECTIVE: Birdshot chorioretinopathy (BC) is an ocular inflammatory disease involving both the retina and the choroid. The study goal was to evaluate indocyanine green angiographic features in BC to assess choroidal involvement. DESIGN: Retrospective, observational case series. PARTICIPANTS: Fifty-two patients with BC documented with at least 1 concomitant fluorescein and indocyanine green angiogram. INTERVENTION: Indocyanine green angiography (ICGA) was performed according to a standard protocol used for inflammatory disorders. MAIN OUTCOME MEASURE: Indocyanine green angiographic signs were correlated with fundus photographs, fluorescein angiography, degree of inflammatory activity, and stage of disease. RESULTS: In active disease, three main features were observed. The principal finding, found in 100% of patients, was the presence of hypofluorescent dark dots during the intermediate phase of angiography; their evolutionary pattern was twofold, becoming either isofluorescent or remaining hypofluorescent at the late phase of angiography. The other two signs were fuzzy, indistinct choroidal vessels and late-diffuse choroidal hyperfluorescence. In chronic longlasting disease, the characteristic finding was the presence of hypofluorescent dark dots that persisted in the late phase of disease and is theorized to correspond either to chorioretinal atrophy (irregular geographic pattern) or to persistent choroidal granulomas (round oval form). CONCLUSIONS: Consistent ICGA findings in 52 patients allowed the authors to establish a fairly precise ICGA semiology for BC. This procedure enabled the authors to assess choroidal involvement, and, in selected cases, it also was found to be of diagnostic help and useful to monitor therapeutic intervention.

[Retinal detachment following YAG laser section of vitreous strands. Apropos of 3 cases]. / Décollement de rétine après tentative de section de brides vitréennes au laser YAG. A propos de 3 cas.

PURPOSE: Retinal detachment after Nd: YAG laser vitreolysis is rarely reported. The pathogenic role of Nd: YAG laser is analyzed from 3 cases of severe retinal detachment. METHODS: Three men aged (40 to 59 years old) had one or more risk factors for retinal detachment: myopia, complicated cataract surgery, personal or family history of retinal detachment. Nd: YAG laser treatment onto vitreous strand was performed because of: retinal traction, repeated vitreous hemorrhage, anterior vitreous strand in a aphakic patient with cystoid macular edema. Within six weeks following Nd: YAG laser vitreolysis, severe retinal detachment with several tears occurred, complicated with proliferative vitreoretinopathy in two patients, and with choroidal hemorrhage in one. In two cases, several surgical procedures with silicon oil were required and visual acuity remained under 20/1000. In the last case retinal reattachment was obtained with scleral buckling and cryopexy, the patient recovered a visual acuity of 20/100 with a macular pucker. DISCUSSION: Retinal detachment occurred shortly after laser YAG vitreolysis. We assumed Nd: YAG laser was possibly responsible and investigated the possible mechanisms: direct retinal tear, vitreous strand traction, side effect of intraocular shock wave. CONCLUSION: Nd: YAG laser vitreolysis seems to be able to cause retinal detachment. Its use is therefore not recommended, particularly in patients at risk, especially since the efficacy of this treatment has not been proved.

Macular serous retinal detachment caused by subretinal leakage in tilted disc syndrome.

OBJECTIVE: To describe a previously unreported complication of tilted disc syndrome: serous retinal detachment, caused by subretinal leakage, that mimics chronic idiopathic central serous chorioretinopathy (ICSC). DESIGN: Retrospective cohort study. PARTICIPANTS: Five patients (five eyes) participated. MAIN OUTCOME MEASURES: Fluorescein angiographic features were measured. RESULTS: All patients presented with visual loss and metamorphopsia. Fundus examination showed features typical of tilted disc syndrome, including obliquely directed long axis of the disc, situs inversus, retinal pigment epithelium conus, hypopigmentation and staphylomatous ectasia inferonasal to the optic disc, as well as a serous retinal detachment. Fluorescein angiography showed a site of leakage or multiple focal areas of staining and atrophy of the retinal pigment epithelium that correlated to the linear pigmentary changes observed at the junction with the inferior staphyloma. The fluorescein angiographic pattern was very similar to that of chronic ICSC. Spontaneous healing occurred in one case, and successful photocoagulation of the site of leakage was applied in two cases; two eyes could not be photocoagulated because of diffuse leakage in the macular region. CONCLUSIONS: To the authors' knowledge, macular serous retinal detachment due to subretinal leakage has not been reported as a complication of tilted disc syndrome. The authors hypothesize that choriocapillary and pigment epithelial disturbances at the junction of the inferior staphyloma permit the subretinal leakage, but the pathogenesis of this complication remains unclear. A study of larger series of such patients is needed to identify the most appropriate management of these cases, which first need to be differentiated from a chronic form of ICSC.

Indocyanine green angiographic features of pathologic myopia.

PURPOSE: To analyze indocyanine green angiographic findings of pathologic myopia and compare them with those of fluorescein angiography, with particular reference to the usefulness of indocyanine green angiography in the management of neovascular complications. METHODS: Thirty-two consecutive patients (52 eyes) with pathologic myopia underwent a complete ophthalmologic examination including fluorescein and indocyanine green angiography. RESULTS: Retrobulbar arteries and veins were visualized solely on indocyanine green angiography in 33 (63%) of 52 eyes. Choroidal arteries appeared attenuated and reduced in number. In the area of staphyloma, choroidal veins were less numerous, and in all eyes an absence of the normal choroidal flush caused by the choriocapillaris filling was observed. Subretinal and retinal hemorrhages were present in 28 (54%) of 52 eyes. Choroidal neovascularization was diagnosed in 16 eyes on fluorescein angiography and in 18 eyes on indocyanine green angiography. In seven eyes, indocyanine green angiography disclosed lacquer cracks (without choroidal neovascularization), appearing in the late phases as hypofluorescent lines, as the probable cause of the subretinal and retinal hemorrhages. In only one eye did indocyanine green angiography fail to disclose choroidal neovascularization detectable on fluorescein angiography. In two eyes, neither dye could clarify the origin of the hemorrhages. CONCLUSIONS: Indocyanine green angiography allows identification of retrobulbar arteries and veins, and analysis of the altered choroidal vasculature. Moreover, indocyanine green angiography is a useful diagnostic tool to differentiate lacquer cracks from choroidal neovascularization in retinal and subretinal hemorrhages.

Retinal vascular changes in congenital hypertrophy of the retinal pigment epithelium.

BACKGROUND: Congenital hypertrophy of the retinal pigment epithelium (CHRPE) is a well-defined clinical entity with usually well-delineated, pigmented oval or round lesion with smooth or scalloped margins. Occasional retinal vascular changes have been reported previously. PURPOSE AND METHOD: To assess the prevalence of these changes, the authors performed a retrospective analysis of 12 patients with CHRPE, for whom fluorescein angiography allowed visualization of the entire lesion and of the retinal vascular capillary bed. RESULTS: Retinal vascular changes were found in 11 (91%) of these 12 patients. The changes consisted of capillary rarefaction in all 11 patients, with areas of capillary nonperfusion exceeding 1 disc diameter (DD) in three patients (25%), micro-aneurysmal capillary dilatations in three (25%), and chorioretinal anastomosis in one. CONCLUSION: These results suggest that the above changes could constitute clinical and angiographic characteristics of CHRPE and allow easy corroboration of its diagnosis, thus avoiding the need for further clinical investigations.

[Retinal detachment following posterior capsulotomy using Nd:YAG laser. Retrospective study of 144 capsulotomies]. / Décollement de rétine après capsulotomie postérieure au laser Nd:YAG. Etude rétrospective de 144 capsulotomies.

Nd:YAG capsulotomy is currently performed after extracapsular cataract surgery and seems to increase the risk of postoperative retinal detachment. In order to evaluate the incidence of this complication in our experience, we retrospectively studied 144 patients who underwent Nd:YAG laser posterior capsulotomy with at least a six-month follow-up. Six patients out of 144 (4.16%) subsequently developed rhegmatogenous retinal detachment. The average time from extracapsular cataract surgery to YAG capsulotomy was 21 months (11 to 26 months). The average time from capsulotomy to retinal detachment was 3.6 months (1 to 8 months). In 4 out of 6 eyes, at least one risk factor for retinal detachment was present (myopia, lattice degeneration, retinal detachment in the fellow eye). Vitreous cells were observed in 4 patients after capsulotomy. In 2 patients, a prophylactic laser photocoagulation had been previously performed. These retinal detachments were not different from aphakic or pseudophakic detachment, but the examination of retinal periphery was particularly difficult because of the peripheral capsular fibrosis, hiding retinal tears in 4 eyes. Two cases of moderate proliferative vitreoretinopathy were observed. Retinal reattachment surgery was successful in all cases with one procedure. The YAG laser energy required to create a capsulotomy was less than that reported in the literature, and no relationship could be established with the total energy applied. Nd:YAG capsulotomy seems to moderately increase the risk of retinal detachment, especially in myopic patients. The mechanisms of vitreous and retinal damage after Nd:YAG capsulotomy are discussed.

The dark choroid in systemic argyrosis.

Argyrosis is a cutaneous discoloration caused by silver. Ocular involvement, including conjunctival and corneal discoloration, has been previously reported. To our knowledge, a retinal involvement was never reported and no data is available about fluorescein angiography patterns of patients with argyrosis. Fluorescein angiography was performed in six consecutive patients with iatrogenic systemic argyrosis. A dark choroid was observed in each case. Red light monochromatic pictures disclosed a leopard spot pattern on the fundus, which was more clearly revealed in one patient by infrared light pictures. These findings suggest that the silver deposit in Bruch's membrane may be responsible for the obscuration of choroidal fluorescence during dye transit and for the visualization of choriocapillary units in pictures using long-wavelength light. The dark choroid is not only present in central retinal dystrophies, but may be observed in other conditions, such as systemic argyrosis.

Ocular fluorophotometric and angiographic findings in toxemia of pregnancy.

Ocular fluorophotometry was performed in 24 patients with hypertension due to toxemia of pregnancy and in ten normal subjects. Patients showing features of accelerated hypertension in the fundus (eg, hemorrhage, cotton-wool spots, and disc edema) were excluded from the study. Fluorescein concentrations in the aqueous and posterior vitreous increased significantly in toxemic patients compared with those in normal subjects; the blood-aqueous barrier was disrupted earlier than the blood-retinal barrier. Nevertheless, these barriers were only disrupted when the arterial diameter was altered. Ocular fluorometric abnormalities disappeared after delivery in all but two cases.