Non-immediate drug hypersensitivity reactions secondary to intravitreal anti-vascular endothelial growth factors.

PURPOSE: To describe a series of non-immediate drug hypersensitivity reactions after intravitreal anti-vascular endothelial growth factors (anti-VEGFs). PATIENTS AND METHODS: Retrospective report of 6 patients with cutaneous non-immediate drug hypersensitivity reactions following intravitreal anti-VEGF injections, 4 after ranibizumab, 1 after bevacizumab and 1 after aflibercept. RESULTS: Clinical manifestations ranged from mild maculopapular rash, purpura to severe generalized erythroderma, with or without systemic involvement such as microscopic hematuria and proteinuria or fever. In two out of the six patients, reintroduction of either the same or an alternative anti-VEGF drug did induce a recurrence of the drug hypersensitivity reaction, while 4 patients showed no recurrence. CONCLUSION: Cutaneous non-immediate drug hypersensitivity reactions secondary to intravitreal anti-VEGF may occur. Continuation of the same drug or switch to another anti-VEGF may either induce recurrence or be well supported by the patient. The decision of drug discontinuation should be guided by the severity of the disease.

Recurrent Macular Edema in Central Retinal Vein Occlusion Treated with Intravitreal Ranibizumab using a Modified Treat and Extend Regimen.

BACKGROUND: The aim of this study was to evaluate the stability over time of the individually defined interval of intravitreal ranibizumab injection (IVR) for the treatment of recurrent macular edema (ME) in central retinal vein occlusion (CRVO). PATIENTS AND METHODS: A case series of treatment naïve patients followed in the Jules Gonin Eye Hospital for macular edema due to central retinal vein occlusion is presented. Patients were treated monthly with IVR until complete absence of fluid on qualitative SD-OCT with a minimum of 5 monthly IVR. Thereafter, they were followed according to a modified treat and extend regimen (mTER). RESULTS: Twelve eyes (12 patients) with ME due to CRVO were included. The mean follow-up period was 31.3 months. Analysis showed that best corrected visual acuity (BCVA), central macular thickness and qualitative spectral domain optical coherence tomography (SD-OCT) showed comparable results under monthly interval, after titration of an individualized interval and when performed in a series. 78% of treating intervals were within ±2 weeks of the first individually adjusted interval. The mean first defined interval was 4.3 weeks and the mean interval over time was 5.5 weeks (p=0.003). There was a trend towards longer interval over time. CONCLUSION: The adjusted interval of retreatment of patients with ME due to CRVO showed a high stability with a trend toward longer duration over time. An mTER regimen seems to be valuable to follow patients with ME with good stabilization of VA.

The effect of switching ranibizumab to aflibercept in refractory cases of macular edema secondary to ischemic central vein occlusion.

BACKGROUND: Macular edema resulting from central retinal vein occlusion is effectively treated with anti-vascular endothelial growth factor injections. However, some patients need monthly retreatment and still show frequent recurrences. The purpose of this study was to evaluate the visual and anatomic outcomes of refractory macular edema resulting from ischemic central retinal vein occlusion in patients switched from ranibizumab to aflibercept intravitreal injections. PATIENTS AND METHODS: We describe a retrospective series of patients followed in the Medical Retina Unit of the Jules Gonin Eye Hospital for macular edema due to ischemic central retinal vein occlusion, refractory to monthly retreatment with ranibizumab, and changed to aflibercept. Refractory macular edema was defined as persistence of any fluid at each visit one month after last injection during at least 6 months. All patients had to have undergone pan-retinal laser scan. RESULTS: Six patients were identified, one of whom had a very short-term follow-up (excluded from statistics). Mean age was 57±12 years. The mean changes in visual acuity and central macular thickness from baseline to switch were +20.6±20.3 ETDRS letters and -316.4±276.6 µm, respectively. The additional changes from before to after the switch were +9.2±9.5 ETDRS letters and -248.0±248.7 µm, respectively. The injection intervals could often be lengthened after the switch. CONCLUSIONS: Intravitreal aflibercept seems to be a promising alternative treatment for macular edema refractory to ranibizumab in ischemic central retinal vein occlusion.

Two-year outcome of an observe-and-plan regimen for neovascular age-related macular degeneration: how to alleviate the clinical burden with maintained functional results.

PURPOSE: The purpose of this study was to report the 2-year outcome of an individually tailored 'observe-and-plan' treatment regimen for neovascular age-related macular degeneration (nAMD), and to investigate its clinical value in terms of functional outcome. This regimen aimed to reduce the clinical burden (visits) by employing individually fixed injection intervals, based on the predictability of an individual's need for retreatment. METHODS: This prospective case series included 104 patients (115 eyes) with nAMD. Following three loading doses of ranibizumab, the disease recurrence interval was determined in monthly observation visits. Retreatment was applied in a series of three injections with individually fixed intervals (2 weeks shorter than the recurrence interval), combined with periodic adjustment of the intervals. The allowed injection intervals in treatment plans ranged from 1 to 3 months. If there was no recurrence at 3 months, the patient could change to monitoring alone. RESULTS: Mean visual acuity (VA) improved by 8.7, 9.7, and 9.2 letters at months 3, 12, and 24, respectively. The mean number of injections was 7.8 and 5.8 during years 1 and 2, respectively, whereas the mean number of ophthalmic examinations was 4.0 and 2.9, respectively. The mean treatment interval (after the loading doses) was 2.0 months during year 1, and 2.2 months during year 2. CONCLUSION: The observe-and-plan regimen significantly improved and maintained VA over the course of 2 years. This favourable functional outcome was achieved with fewer clinic visits compared with other regimens. Therefore, this observe-and-plan regimen has the potential to alleviate the clinical burden of nAMD treatment.

Comparison of fundus autofluorescence images acquired by the confocal scanning laser ophthalmoscope (488 nm excitation) and the modified Topcon fundus camera (580 nm excitation).

To compare autofluorescence (AF) images obtained with the confocal scanning laser ophthalmoscope (using the Heidelberg retina angiograph; HRA) and the modified Topcon fundus camera, in a routine clinical setting. A prospective comparative study conducted at the Jules-Gonin Eye Hospital. Fifty-six patients from the medical retina clinic. All patients had complete ophthalmic slit-lamp and fundus examinations, colour and red-free fundus photography, AF imaging with both instruments, and fluorescein angiography. Cataract and fixation were graded clinically. AF patterns were analyzed for healthy and pathological features. Differences of image noise were analyzed by cataract grading and fixation. A total of 105 eyes were included. AF patterns discovered by the retina angiograph and the fundus camera images, respectively, were a dark optic disc in 72 % versus 15 %, a dark fovea in 92 % versus 4 %, sub- and intraretinal fluid visible as hyperautofluorescence on HRA images only, lipid exudates visible as hypoautofluorescence on HRA images only. The same autofluorescent pattern was found on both images for geographic atrophy, retinal pigment changes, drusen and haemorrhage. Image noise was significantly associated with the degree of cataract and/or poor fixation, favouring the fundus camera. Images acquired by the fundus camera before and after fluorescein angiography were identical. Fundus AF images differ according to the technical differences of the instruments used. Knowledge of these differences is important not only for correctly interpreting images, but also for selecting the most appropriate instrument for the clinical situation.

Intravitreal ranibizumab in the treatment of predominantly hemorrhagic lesions in exudative age-related macular degeneration.

BACKGROUND: Submacular hemorrhage is a manifestation of neovascular age-related macular degeneration (AMD) that has a very poor natural history leading to severe visual loss. We have evaluated the safety and efficacy of intravitreal ranibizumab in the treatment of predominantly hemorrhagic AMD. PATIENTS AND METHODS: A retrospective study of patients with predominantly hemorrhagic AMD treated with intravitreal ranibizumab at the Jules Gonin Eye Hospital between December 2006 and December 2008 was undertaken. Baseline and monthly follow-up exams included visual acuity (VA), fundus exam and optical coherence tomography (OCT) while fluorescein and indocyanine green angiography were performed at least every three months. RESULTS: The study included 8 eyes. The mean follow-up was 13 months (SD: 6.3). The mean number of intravitreal injections administered for each patient was 6.4 (SD: 2). 50 % of the patients demonstrated stable or improved VA. The size of hemorrhage at baseline was inversely correlated to the final VA (two-tailed p value = 0.038) and positively correlated to the final central macular thickness (two-tailed p value = 0.021). Anticoagulation treatment was inversely correlated to the time of hemorrhage resolution (two-tailed p value = 0.039). CONCLUSIONS: Intravitreal ranibizumab may be an effective treatment for predominantly hemorrhagic lesions due to neovascular AMD.

Genotype-phenotype correlation of age-related macular degeneration: influence of complement factor H polymorphism.

BACKGROUND/AIMS: Complement factor H (CFH) Y402H polymorphism shows a strong association with age-related macular degeneration (AMD). Although the phenotypic concordance of AMD has been shown in sibling/twin studies, little is known about the genotype-phenotype association. In this study, we investigated whether CFH Y402H is associated with early phenotypic features. METHODS: Statistical analysis was performed on 420 patients with AMD with complete clinical and genetic data (graded colour fundus photographs, according to the International Classification and Grading System for AMD and successful testing for CFH Y402H). RESULTS: In this Swiss population, an OR of 2.95 was confirmed for AMD in the presence of at least one risk C allele and OR of 9.05 for the CC homozygotes, corrected for age and sex. No difference was found between the AMD stages. Patients homozygous for the risk allele showed significant association with peripheral drusen (p = 0.028) and for central drusen location (p = 0.049). No trend was found for other drusen criteria (size, total surface, location nasal to disc) and for pigmentary changes. CONCLUSIONS: The CFH Y402H polymorphism showed a genotype-phenotype association for some drusen features. Additional genetic factors are likely to influence drusen phenotype.

Interferon-associated retinopathy--a case report.

BACKGROUND: Interferon alpha is used for treatment in oncology and for chronic hepatitis C. Interferon-associated retinopathy is not infrequent and typically includes cotton wool spots, haemorrhages, rarely macular or papillary oedema, capillary non-perfusion and sometimes retinal or even choroidal vascular occlusion. The latter may be irreversible, while uncomplicated forms are usually reversible. We report an atypical case of interferon-associated retinopathy, associated with microaneurysms, Roth spots, and retinal pigment changes. HISTORY AND SIGNS: A 63-year-old asymptomatic patient presented with partially white centred, flame-shaped haemorrhages, some cotton wool spots and microaneurysms on both fundi. In addition, the left eye presented chronic pigment epithelium abnormalities surrounding the fovea without signs of exudation, most likely secondary to a previous central retinal exudative detachment combined with choroidal hypoperfusion. Interferon alpha 2a therapy for chronic hepatitis C had been given for 6 months. He was known for arterial hypertension (risk factor), mild microcytic anaemia and mild glucose intolerance, which may be responsible for some unusual features of the retinopathy. THERAPY AND OUTCOME: The patient was closely followed, while the interferon therapy was continued on reduced dosage. No vision-threatening complication was observed. CONCLUSIONS: Interferon-associated retinopathy may show atypical features. Early diagnosis and careful follow-up are recommended in order to avoid progression to irreversible changes. Dose-reduction or even interruption of interferon treatment needs to be considered in cases of interferon-associated retinopathy.

Retinal angiomatous proliferation treated with a combination of intravitreal triamcinolone acetonide and photodynamic therapy with verteporfin.

PURPOSE: Retinal angiomatous proliferation (RAP) is a particularly aggressive form of exudative age-related macular degeneration. Response to laser photocoagulation or to photodynamic therapy (PDT) alone is often disappointing. The purpose of this study was to determine whether intravitreal triamcinolone acetate (TA) injections followed by PDT in eyes with early stage RAP may be effective. METHODS: Prospective uncontrolled study, enrolling 11 patients (11 eyes) with stage 2 RAP, treated with intravitreal TA injection followed by PDT. Patients with large pigment epithelium detachment, RAP stage 3, or pre-existing glaucoma and known steroid responders were excluded. All patients underwent a complete ophthalmic examination including fluorescein and indocyanine green (ICG) angiography and optical coherence tomography (OCT-3) at baseline and at 1, 3, 6, and 12 months. Informed consent was obtained from all patients. RESULTS: Mean follow-up was 14.9 months (range 6 C21 months). Mean age was 82 years. In four patients a small pigment epithelium detachment was found on tomography. Initial visual acuity (VA) ranged from 0.1 to 0.6 on the Snellen scale. After calculating the logarithmic values the authors found an initial mean VA of logMAR 0.61, which improved by 1.5, 0.9, and 0.9 log lines after 3, 6, and 12 months, respectively. Although the VA gain from baseline tended to decrease with time, only 2 patients (18%) had an actual loss of acuity>or=3 lines). Retreatment was required in 5 eyes. CONCLUSIONS: In this prospective pilot study examining the use of intravitreal TA followed by PDT with verteporfin in eyes with stage 2 RAP, without a large pigment epithelium detachment, the authors found a potential benefit in terms of stabilization or even improvement of vision.

[Optical coherence tomography in Malattia Leventinese]. / Tomographie a coherence optique dans la Malattia leventinese.

BACKGROUND: Malattia Leventinese (ML) is a genetically homogeneous macular dystrophy with an autosomal dominant mode of inheritance. Ophthalmoscopically it is recognisable by a radial pattern of drusen-like deposits in the macula and by parapapillary deposits, named Forni's verrucosities. The aim of this study is to describe optical coherence tomographic (OCT) findings and to compare them with histological data. PATIENTS AND METHODS: Six patients underwent ophthalmological examination, angiography and OCT. Diagnosis was confirmed by genetic analysis of the R345W mutation. A histopathological study of an ML donor eye was performed. RESULTS: OCT revealed a diffuse RPE-choriocapillaris thickening with nodular features in the macular and parapapillary areas. The protrusions reached as far as the outer nuclear layer. CONCLUSIONS: OCT is a non-invasive technique that provides a cross-sectional picture of the retina comparable to a histological section. In ML, OCT revealed a diffuse alteration of the RPE-Bruch's membrane complex. The macular and parapapillary nodular lesions are the tomographic equivalents of drusen and Forni's verrucosities.

Subretinal choroidal neovascularization associated with choroidal nevus.

PURPOSE: Evaluation of a large series of choroidal nevi inducing the formation of a neovascular membrane in order to more clearly define the clinical presentation and to evaluate the efficacy of various treatment options. METHOD: Retrospective study of 22 clinical cases. RESULTS: All nevi were situated in the posterior choroid. They had a mean diameter of 3.8 mm and a mean thickness of 1.4 mm. Neovascular membranes were classic in all cases, extrafoveal in 13 cases (59%), and subfoveal in 9 cases (41%). A serous retinal detachment was present in every case, hemorrhages were present in 13 cases (59%), and lipid deposits were present in 16 cases (73%). All extrafoveal neovascular membranes were successfully treated by thermal laser photocoagulation. Initial visual acuity was 0.1 in three cases, 0.2-0.4 in five cases, 0.5-0.8 in four cases, and 1.0 or more in two cases. Final visual acuity was 0.1 in one case, 0.2-0.4 in one case, 0.5-0.8 in four cases, and 1.0 or more in seven cases. Five subfoveal neovascular membranes were treated either by thermal laser, photodynamic therapy, or irradiation. No treatment was applied in four cases and in one of these cases, spontaneous resolution of the neovascular membrane was observed. No growth of the pigmented tumor was observed with a mean follow-up of 4.8 years. CONCLUSIONS: Proliferation of a neovascular membrane on the surface of a pigmented choroidal tumor is a rare complication and is considered to be a relative indicator of a benign nature of the lesion. In the authors' experience, neovascular membranes are extrafoveal in more than half of cases and are accessible to laser photocoagulation. In contrast, the various modalities used to treat subfoveal neovascular membrane were ineffective and functional prognosis was unfavorable in these cases.

Juvenile neuronal ceroid lipofuscinosis (Batten disease) CLN3 mutation (Chrom 16p11.2) with different phenotypes in a sibling pair and low intensity in vivo autofluorescence.

BACKGROUND: The neuronal ceroid lipofuscinoses (Batten disease) are a heterogeneous group of autosomal recessively inherited disorders causing progressive neurological failure, mental deterioration, seizures and visual loss secondary to retinal dystrophy. The juvenile type is of special interest to the ophthalmologist as visual loss is the earliest symptom of the disorder. HISTORY AND SIGNS: We present two siblings with severe retinal dystrophy due to juvenile Batten disease. Sibling A (age 10) presented with visual loss, photophobia and night blindness, starting at age 4. His vision was perception of light by the age of 10.5 years. Fundus examination revealed severe pigmentary retinopathy. Sibling B (age 7) presented with night vision difficulties. Fundus examination revealed a bull's eye maculopathy with minimal peripheral atrophic changes. In vivo autofluorescence level was found to be very low. Electroretinography (ERG) showed generalized retinal dysfunction involving both cone and rod systems, with an electronegative maximal response. In both siblings vacuolated lymphocytes were found on a peripheral blood film and on molecular genetic testing both were homozygous for the commonly reported 1.02-kb deletion of the CLN3 gene. THERAPY AND OUTCOME: Although there is no effective treatment, the early diagnosis allowed accurate genetic and social counseling. CONCLUSIONS: Juvenile Batten disease should be considered in children with a retinal dystrophy, especially where there is a bull's eye maculopathy and an abnormal full field ERG. The novel finding of very low in vivo autofluorescence is consistent with histopathological studies and may be secondary to photoreceptor cell loss.

[Photocoagulation of the retinal feeder vessels of a chorioretinal anastomosis in age-related macular degeneration]. / Photocoagulation des vaisseaux rétiniens nourriciers d'une anastomose choriorétinienne dans le cadre d'une dégénérescence maculaire liée à l'âge.

The presence of a chorioretinal anastomosis in the setting of age-related macular degeneration is known as a sign of poor prognosis. No treatment has proven to be effective. We describe a 71-year-old female patient presenting with exudative age-related macular degeneration, a chorioretinal anastomosis with two retinal feeder vessels (arteriole and veinule), a serous retinal pigment epithelium detachment, and a suspected early subretinal neovascular membrane. She was treated with ICG-guided laser photocoagulation directed to the hot spot, with treatment-zone enlargement directed to the retinal feeder vessels and followed up for 6 months. Although a second laser treatment for the reperfused subretinal neovascular membrane was needed, the clinical and angiographic end result was beneficial. Visual acuity improved by two lines, the chorioretinal anastomosis was occluded, and the pigment epithelium reattached. Taking into account the low therapeutic success rate described in the literature, we suggest that the specific treatment of the retinal feeder vessels, which to our knowledge has not been described before, may be a valuable treatment option.

A simple treatment for chronic postoperative hypotony of unknown etiology: the injection of balanced salt solution into the anterior chamber.

Postoperative hypotony is not rare. When it occurs, effective treatment must be initiated to avoid secondary complications. We report two cases of postoperative hypotony that have been treated successfully with a single injection of balanced salt solution (BSS) into the anterior chamber. One patient developed hypotony three months after combined cataract surgery and trabeculectomy with the use of Mitomycin C (MMC). The cause of hypotony remained unknown. Leakage, hyperfiltration, cyclodialysis, and other possible causes had been excluded. With a single injection of BSS into the anterior chamber the long-standing hypotony was successfully managed. A second patient with hypotony after pars plana vitrectomy was also treated successfully with an injection of BSS into the anterior chamber. We conclude that an injection of BSS into the anterior chamber is an inexpensive and efficacious remedy for postoperative hypotony of unknown etiology.