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.

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.

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.

Quantitative evaluation of fluorescein angiograms: microaneurysm counts.

This study describes a method for quantifying microaneurysms (MA) from fluorescein angiograms. The method was validated by the reproducibility of the number of MA in 30 angiograms read twice each by two independent observers; and by the absolute difference in MA counts between two readings by the same observer, and difference in numbers counted by two different observers. The precise location of each MA on two readings was also studied and the reproducibility of location varied from 60 to 71%, depending on the quality of the angiograms. Clinicians and technicians working in the same or in different centers obtained similar results. The coefficient of correlation between observers and between readings was satisfactory, r greater than 0.9. The method is easy to learn and the reproducibility allows for its use in clinical trials.

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.

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 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.

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.

[Fluorescence angiography: personal technics of automatized development of films and printing]. / L'angiographie en fluorescence : nos techniques sur le développement automatisé des films et le tirage.

The film of an angiography by fluorescence presents specific particular characteristics. Treatment of the film has to be adapted to these particularities, and the chemical products used have to be specially chosen. In this way, the results obtained can be greatly improved. The procedure can be automatized by the use of a simple apparatus, and printing on paper causes no particular difficulty.

[Retinal congenital arterial loop and hemorrhage of the vitreous (author's transl)]. / Boucle artérielle rétinienne congénitale et hémorragie du vitré.

In five young adults, mild vitreous hemorrhage occurred from the area of retinal loops near or on the optic nerve. In all cases, the hemorrhage cleared without further complications. This vascular congenital malformation may be associated with secondary complications more frequently than has previously been reported.

[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.

[Diffuse retinal epitheliopathy and central serous chorioretinopathy]. / Epithéliopathie rétinienne diffuse et choriorétinopathie séreuse centrale.

Follow-up examinations were conducted in 27 patients (51 eyes) affected by diffuse retinal pigment epitheliopathy (D.R.P.E.), over an average period of 37 months. This disease associates multiple subretinal foci of leakage resulting in retinal serous detachments (R.S.D.), often widespread alterations in retinal pigment epithelium, and frequent small serous detachments of retinal pigment epithelium. The course is chronic and recurrence of subretinal leakage is common. Involvement of macular pigment results in poor long-term visual prognosis. Features of these patients were compared with those of 138 patients affected by central serous choroidopathy (C.S.C.). Both D.R.E.P. and C.S.C. are more frequent in males, and demonstrate subretinal leakages and transient retinal serous detachments. Nevertheless, numerous data differentiate these two diseases, D.R.P.E. being detected at a later age (49 years) than C.S.C. (39 years). Bilaterality of the affection is more frequent in D.R.E.P. (88 p. cent) while serous detachment is less frequent in D.R.P.E. (31 p. cent) than in C.S.C. (82 p. cent). Small foci of subretinal leakage are present in both diseases but they are frequently multiple, scattered, extra-macular and mainly peripapillary in D.R.P.E.; they are chronic or recurrent and are present usually in an area of pigment epithelium depigmentation. These changes are often vertically oriented downwards towards the inferior periphery of the fundus. In D.R.P.E. there are frequently visual fields defects (70,5 p. cent) corresponding to the area of pigmentary involvement, dyschromatopsy (64 p. cent) and E.O.G. abnormalities (75 p. cent). D.R.P.E. and C.S.C. are two closely related diseases but they differ by the extent and diversity of the pigment epithelium lesions functional impairment, and visual prognosis. Photocoagulation of leaking spots resulting in macular detachment appears to be justified as in C.S.C. Long-term prognosis depends on the degree of extension of pigmentary changes into the macular area.

[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.

[Multifocal vitelliform dystrophy : a case report (author's transl)]. / Disques vitelliformes multiples. a propos d'un cas.

A case of multiple vitelliform dystrophy is described in an adult white woman ; vision, angiography, EOG are the same as in true Best's disease, but the reduction of vision seams more severe and occurs earlier. The extramacular discs are smaller, faster in evolution, they can appear, disappear or coalesce as in our case. The disease is genetically much less demonstrative than central vitelliform dystrophy. Angiographically, besides the usual pattern, they shaw marked staining without evidence of subretinal neovascularization perhaps due to a slight alteration of a still living RPE, and a hollow aspect of the discs at the level of RPE on stereo-angiograms. This is to be compared with the pathological findings made by Gass who described a marked thinning of the RPE.

[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.

[Pan-retinal argon laser-photocoagulation in retinopathia diabetica. First results (author's transl)]. / Panretinale Laserkoagulation bei Retinopathia diabetica. Erste Resultate.

The apparition of diabetic retinopathy depends on the duration of the evolution of the diabetes and its control, and its type. The indications for photocoagulation are in progressive retinopathy the existence of macular edema or retinal or prepapillar neovascularisation. The pan-rtinal argon laser photocoagulation is the best technic for treatment. It leads to a global improvement whose results are presented, after 2 years follow-up.