Long-term outcomes of phakic patients with diabetic macular oedema treated with intravitreal fluocinolone acetonide (FAc) implants.

PURPOSE: Diabetic macular oedema (DMO) is a leading cause of blindness in working-age adults. Slow-release, nonbioerodible fluocinolone acetonide (FAc) implants have shown efficacy in the treatment of DMO; however, the National Institute for Health and Care Excellence recommends that FAc should be used in patients with chronic DMO considered insufficiently responsive to other available therapies only if the eye to be treated is pseudophakic. The goal of this analysis was to examine treatment outcomes in phakic patients who received 0.2 µg/day FAc implant. METHODS: This analysis of the phase 3 FAME (Fluocinolone Acetonide in Diabetic Macular Edema) data examines the safety and efficacy of FAc implants in patients who underwent cataract extraction before (cataract before implant (CBI) group) or after (cataract after implant (CAI) group) receiving the implant. The data were further examined by DMO duration. RESULTS: Best corrected visual acuity (BCVA) after 36 months was comparable in the CAI and CBI groups. Both the percentage of patients gaining ≥ 3 lines of vision and mean change in BCVA letter score were numerically greater in the CAI group. In addition, most patients who underwent cataract surgery experienced a net gain in BCVA from presurgery baseline as well as from original study baseline. CONCLUSIONS: These data support the use of 0.2 µg/day FAc implants in phakic as well as in pseudophakic patients. These findings will serve as a pilot for design of future studies to evaluate the potential protective effect of FAc implants before cataract surgery in patients with DMO and cataract.

Inhibition of viral replication in vitro by antiviral-treated amniotic membrane. Possible use of amniotic membrane as drug-delivering tool.

PURPOSE: To investigate if amniotic membrane (AM) incubated with antivirals can inhibit viral growth in vitro. METHODS: AM samples were incubated with a solution of acyclovir or trifluridine. The treated AM was placed onto monolayers of Vero cells, a continuous cell line from monkey kidney, infected with herpes simplex virus. Viral growth was assessed in comparison to control infected cells by direct examination with an inverted microscope at low magnification for the presence and extension of the typical cytopathic effect, or by estimation of viral genomes. RESULTS: AM soaked in acyclovir or trifluridine inhibited significantly the development of herpes simplex virus in cell cultures, based on the viral growth compared with controls. Non-treated AM did not significantly affect viral replication. CONCLUSIONS: Our preliminary in vitro data show that antiviral-treated amniotic membrane can inhibit viral replication. Therefore, the possibility to combine the previously published anti-inflammatory properties of AM with the capability to absorb antivirals and sustain drug release could be taken into consideration.

Novel mutations in of the ABCR gene in Italian patients with Stargardt disease.

PURPOSE: Stargardt disease (STGD) is the most prevalent juvenile macular dystrophy, and it has been associated with mutations in the ABCR gene, encoding a photoreceptor-specific transport protein. In this study, we determined the mutation spectrum in the ABCR gene in a group of Italian STGD patients. METHODS: The DNA samples of 71 Italian patients (from 62 independent pedigrees), affected with autosomal recessive STGD, were analysed for mutations in all 50 exons of the ABCR gene by the DHPLC approach (with optimization of the DHPLC conditions for mutation analysis) and direct sequencing techniques. RESULTS: In our group of STGD patients, 71 mutations were identified in 68 patients with a detection rate of 95.7%. Forty-three mutations had been already reported in the literature, whereas 28 mutations had not been previously described and were not detected in 150 unaffected control individuals of Italian origin. Missense mutations represented the most frequent finding (59.2%); G1961E was the most common mutation and it was associated with phenotypes in various degrees of severity. CONCLUSIONS: Some novel mutations in the ABCR gene were reported in a group of Italian STGD patients confirming the extensive allelic heterogeneity of this gene-probably related to the vast number of exons that favours rearrangements in the DNA sequence.

A normal electro-oculography in a family affected by best disease with a novel spontaneous mutation of the BEST1 gene.

AIMS: To describe clinical and genetic findings in an Italian family affected by Best disease. METHODS: Five related patients underwent a complete ophthalmological assessment; genetic testing was performed by single-strand conformation polymorphism analysis and direct sequencing of the BEST1 gene. RESULTS: In three of five family members, the sequence analysis of the BEST1 gene revealed a single Phe-to-Leu transition at nucleotide 305 associated with clinical evidence of Best disease. Surprisingly, the electro-oculogram was normal in all affected patients. CONCLUSION: This study reveals a de novo mutation in the BEST1 gene never described before, sustaining the autosomal-dominant pattern of inheritance of the disease. Clinical evaluation showed phenotypic variability between affected members. In addition, these data suggest that a normal electro-oculography (EOG) does not rule out a diagnosis of Best disease, supporting instead the crucial role of molecular analysis.

Atherosclerotic and thrombophilic risk factors in patients with recurrent central retinal vein occlusion.

PURPOSE: Atherosclerotic and thrombophilic risk factors may be causes of central retinal vein occlusion (CRVO). The aim of this study was to evaluate the prevalence of the aforesaid risk factors in patients with recurrent CRVOs and patients with a single episode of CRVO. METHODS: Seventeen patients with recurrent CRVO and 30 with a single episode of CRVO were enrolled. The atherosclerotic risk factors investigated were hypertension, diabetes, smoking, and dyslipidemia. Specific laboratory tests for the following thrombophilic markers were performed: homocystinemia (Hcy), lipoprotein (a), factor VIII, factor II G20210A and factor V G1691A polymorphisms, lupus anticoagulant, anticardiolipin antibodies, plasminogen activator inhibitor-1, and deficit of vitamins B6, B12, and folic acid. A multivariate analysis, adjusted for age, gender, traditional and thrombophilic risk factors, was performed. Statistical significance was set at p

Phenotypic intrafamilial variability associated with S212G mutation in the RDS/peripherin gene.

PURPOSE: To describe an Italian family in which two separate phenotypes (retinitis pigmentosa and adult onset vitelliform macular dystrophy) are associated with an identical mutation (S212G) in the peripherin/RDS gene. This mutation has already been reported in patients with retinitis pigmentosa, but it has never been previously detected in association with adult onset vitelliform macular dystrophy. METHODS: A 38-year-old woman complained of bilateral mild metamorphopsias and on ophthalmologic examination she showed the clinical phenotype of adult onset vitelliform macular dystrophy. Her 62-year-old mother was clinically diagnosed with a retinitis pigmentosa, with a severe clinical course. RESULTS: In both patients, molecular genetic analysis revealed a 874A-->G transition in the exon 2 of the RDS gene leading to the amino acid change of S212G. CONCLUSIONS: Peripherin/RDS S212G mutation may have damaging effects on the formation and stability of the photoreceptors' disk structure and may be associated with different clinical phenotypes, even in the same family. Intrafamilial phenotypic variability has been reported for other RDS mutations; this supports the possible influence of modifier genes or environmental factors in the clinical expression of RDS gene variants. Moreover, it suggests that in patients with retinal degeneration and peripherin/RDS mutation, caution should be taken both in using molecular genetic results to predict the clinical course of the disease and in offering genetic counseling.

Ocular surface temperature in central retinal vein occlusion: preliminary data.

PURPOSE: To compare ocular surface temperature (OST) measures in patients with central retinal vein occlusion (CRVO) and controls. METHODS: Thirty-six patients with unilateral CRVO and 54 healthy volunteers were included in the study. OST was evaluated by infrared thermography. RESULTS: In CRVO eyes and in fellow, nonaffected eyes, OST values were lower than in controls (p<0.05). Ischemic CRVO eyes showed lower temperatures than nonischemic ones. CONCLUSIONS: Infrared thermography may be helpful in the management of patients with CRVO.

A novel mutation in the VMD2 gene in an Italian family with Best maculopathy.

Vitelliform macular dystrophy (Best disease) is an inherited macular degeneration in which the primary defect is thought to occur at the level of the retinal pigment epithelium. The VMD2 gene, considered responsible for the disease, mapped to the long arm of chromosome 11, and it codifies the bestrophin protein, probably acting as a transmembrane ionic channel. In the present study, we screened for mutations the VMD2 gene in Italian patients with Best maculopathy. Five families with Best disease were recruited from central and southern Italy, and family members were evaluated by complete ophthalmologic examination and DNA analysis by means of DHPLC technology. Some mutations of the VMD2 gene were identified and among them there was a novel mutation (R218G), probably involving a functionally active region of the bestrophin protein. In spite of the small number of families considered, it was possible to note a significant phenotypic heterogeneity. First, in one family the R218C mutation was associated with early onset of choroidal neovascularization (CNV) in the affected mother and her son, while no CNV was reported in another family sharing the same mutation. Then a patient with the R25W mutation showed a multifocal location of the vitelliform deposits, while another family with the same mutation showed a typical isolated vitelliform disc in the macular area.

Intravitreal bevacizumab therapy for choroidal neovascularization secondary to age-related macular degeneration: 6-month results of an open-label uncontrolled clinical study.

PURPOSE: To investigate the 6-month safety and clinical outcomes of intravitreal injections of bevacizumab administered to treat choroidal neovascularization secondary to age-related macular degeneration. METHODS: Twenty-seven patients underwent 1.25 mg intravitreal injections of bevacizumab at baseline. A similar intravitreal injection was administered to all eyes at 1 and 2 month follow-up visits. At baseline and at each follow-up visit (1, 2, 3, and 6 months), patients underwent best-corrected visual acuity (BCVA) measurement, fluorescein angiography, indocyanine green angiography, and optical coherence tomography. Laboratory testing, visual field analyses, and endothelial cell counts were performed at baseline and third and sixth months. RESULTS: At 3 months, the mean BCVA remained substantially stable at 20/100. Mean central retinal thickness (CRT) decreased from 373 to 279 microm (p<0.01). Mean lesion greatest linear dimension (GLD) decreased from 4087 to 3782 microns (p<0.01). At 6 months, mean BCVA slightly decreased from 20/100(-1) to 20/125(-3) (not significant, p=0.40). Mean CRT was still inferior to baseline (305 microm, p<0.01). Mean lesion GLD was 4186 microm, not different from baseline values (p=0.59), but superior to 3-month mean GLD (p<0.01). Significant visual field defects or endothelial cell losses were not detected at 3 and 6 months. Laboratory testing did not reveal any clinically significant deviations compared to baseline values. CONCLUSIONS: Intravitreal therapy using bevacizumab over 6 months showed stabilization of visual acuity and choroidal neovascularization activity; the safety data were convincing.

Quality of vision: A consensus building initiative for a new ophthalmologic concept.

PURPOSE: Many studies have addressed the quantification of visual acuity, and the conventional method of measuring it has so far demonstrated serious limitations. Vision testing requires new methods that can more precisely express the quality of vision as perceived by the patient. METHODS: This study employed the Delphi method of consensus building. Concepts associated with quality of vision (QoV) were identified by a board of experts and proposed to participating specialists in two subsequent questionnaires. Upon receipt of the completed questionnaires, the replies were classified to determine the building blocks of a consensus. RESULTS: By analyzing the replies to the two questionnaires, the authors determined the key elements of QoV on which a consensus was found among the respondents. CONCLUSIONS: A consensus was reached on the opinion that the quantification of visual acuity by traditional means is inadequate for investigating QoV. Although visual acuity is still a basic element for testing, the experts believe that contrast sensitivity, reading speed, and microperimetry are additional parameters necessary for quantifying QoV. The use of a psychometric questionnaire on visual function could allow a better interpretation of visual impairment.

Clear corneal incision of 2.75 mm for cataract surgery induces little change of astigmatism in eyes with low preoperative corneal cylinder.

PURPOSE: To assess the early astigmatic effect induced by 2.75 mm clear cornea incisions with different locations for cataract surgery. METHODS: A total of 146 eyes of different patients were studied prospectively. Cataract surgery was performed by three surgeons, two using a temporal approach and one using a superior approach. For both approaches, the site of the 2.75 mm incision was allowed to vary slightly according to the characteristics of the eye and orbit. Computerized videokeratography was used to measure corneal astigmatism before surgery and after 1, 4, and 12 weeks. Corneal astigmatism was recorded as cylinder and axis and it was then converted to 2 power vector. Model based prediction and comparisons were made for the most commonly used corneal incision sites: 12 (both eyes), 2 (left eye), and 8 (right eye) o'clock meridian. RESULTS: After 3 months the differences in corneal astigmatism (JCC 0 ) between the incisions performed at 12 and 2 o'clock were not statistically significant (-0.08, 95% CI: -0.19, -0.02); the differences in JCC 0 between incisions at 12 and 8 o'clock were -0.17 (95% CI: -0.30, -0.05; p<0.01). After 3 months the change in JCC 0 for the patients with 0.5 D with-the-rule preoperatively were -0.32 (95% CI: -0.44, 0.21; p<0.01) for incisions at 12; -0.24 (95% CI: -0.36, 0.13; p<0.01) for incisions at 2; and -0.15 (95% CI: -0.27, -0.03; p<0.05) for incisions at 8. After 3 months the changes of JCC 0 for the patients with -0.5 D against-the-rule pre-operatively were 0.10 (95% CI: 0.04, 0.23) for incision at 12; 0.18 (95% CI: 0.04, 0.32; p<0.05) for incisions at 2; and 0.27 (95% CI: 0.14, 0.40; p<0.01) for incisions at 8 o'clock. The oblique astigmatic vector (JCC 45 ) was very modest in this sample before surgery and underwent minimal and nonsignificant change after it. CONCLUSIONS: This study has shown that a 2.75 mm clear corneal incision causes a small change of corneal cylinder regardless of incision site.

Occurrence of full-thickness macular hole complicating Stargardt disease with ABCR mutation.

PURPOSE: To report an unusual episode of full-thickness macular hole complicating Stargardt disease with an ABCR mutation. METHODS: Case report . RESULTS: Fundus examination of a 20-year-old healthy man showed typical fundus manifestation with yellowish-round or fish-like flecks associated with vitreous macular adhesion and a round punched-out area in the right eye. Optical coherence tomography (OCT) illustrated a full-thickness macular hole. Molecular genetic examination of the ABCR gene showed two heterozygous missense mutations: R1108C (CGC-->TGC) in exon 22 and a splicing mutation IVS6--> 1GT - described in the literature in association with Stargardt disease. CONCLUSIONS: Macular hole was once described in other inherited retinal degenerations (Best disease and Bietti crystal line retinopathy). The pathogenesis gives rise to a host of speculations: widespread alteration of the retinal pigment epithelium; inflammatory mechanisms; a minor trauma which might cause subretinal fibrosis. Surgical procedures were not performed on our patient after his ophthalmologic history and findings were considered.

Clear corneal incision of 2.75 mm for cataract surgery induces little change of astigmatism in eyes with low preoperative corneal cylinder.

PURPOSE: To assess the early astigmatic effect induced by 2.75 mm clear cornea incisions with different locations for cataract surgery. METHODS: A total of 146 eyes of different patients were studied prospectively. Cataract surgery was performed by three surgeons, two using a temporal approach and one using a superi-or approach. For both approaches, the site of the 2.75 mm incision was allowed to vary slightly according to the characteristics of the eye and orbit. Computerized videokeratography was used to measure corneal astigmatism before surgery and after 1, 4, and 12 weeks. Corneal astigmatism was recorded as cylinder and axis and it was then converted to 2 power vector. Model based prediction and comparisons were made for the most commonly used corneal incision sites: 12 (both eyes), 2 (left eye), and 8 (right eye) oclock meridian. RESULTS: After 3 months the differences in corneal astigmatism (JCC 0 ) between the incisions performed at 12 and 2 oclock were not statistically significant (-0.08, 95% CI: -0.19, -0.02); the differences in JCC 0 between incisions at 12 and 8 oclock were -0.17 (95% CI: -0.30, -0.05; p<0.01). After 3 months the change in JCC 0 for the patients with 0.5 D with-the-rule preoperatively were -0.32 (95% CI: -0.44, 0.21; p<0.01) for incisions at 12; -0.24 (95% CI: -0.36, 0.13; p<0.01) for incisions at 2; and -0.15 (95% CI: -0.27, -0.03; p<0.05) for incisions at 8. After 3 months the changes of JCC 0 for the patients with -0.5 D against-the-rule pre-operatively were 0.10 (95% CI: 0.04, 0.23) for incision at 12; 0.18 (95% CI: 0.04, 0.32; p<0.05) for incisions at 2; and 0.27 (95% CI: 0.14, 0.40; p<0.01) for incisions at 8 oclock. The oblique astigmatic vector (JCC 45 ) was very modest in this sample before surgery and underwent minimal and nonsignificant change after it. CONCLUSIONS: This study has shown that a 2.75 mm clear corneal incision causes a small change of corneal cylinder regardless of incision site.

Fluorescein angiography and indocyanine green angiography for identifying occult choroidal neovascularization in age-related macular degeneration.

PURPOSE: To assess whether fluorescein angiography (FA) alone without indocyanine green angiography (ICGA) can identify and localize occult choroidal neovascularization (CNV) in age-related macular degeneration (ARMD). METHODS: Seventy-nine eyes of 77 consecutive patients with occult CNV were evaluated independently by two skilled physicians at first with FA alone and then with FA combined with ICGA by fundus camera. RESULTS: The agreement between FA and ICGA was 73% and 68% for the two physicians (K=0.585 and 0.512, respectively). The first operator correctly identified 20/27 as plaque CNV; six had different sizes and locations. The second operator identified 25/30, with one mistaken for size and location. For focal CNV the first operator identified 34/39, and the second one 23/35. CONCLUSIONS: Comparing the FA results with ICGA, CNV was correctly identified in about 60% of cases. Therefore, ICGA should be considered an indispensable diagnostic test to identify the presence, the type, and the location of occult CNV.

Fluorescein angiography and indocyanine green angiography for identifying occult CNV in ARMD.

PURPOSE: To assess whether fluorescein angiography (FA) alone without indocyanine green angiography (ICGA) can identify and localize occult choroidal neovascularization (CNV) in age-related macular degeneration (ARMD). METHODS: Seventy-nine eyes of 77 consecutive patients with occult CNV were evaluated independently by two skilled physicians at first with FA alone and then with FA combined with ICGA by fundus camera. RESULTS: The agreement between FA and ICGA was 73% and 68% for the two physicians (K=0.585 and 0.512, respectively). The first operator correctly identified 20/27 as plaque C N V; six had different sizes and locations. The second operator identified 25/30, with one mistaken for size and location. For focal CNV the first operator identified 34/39, and the second one 23/35. CONCLUSIONS: Comparing the FA results with ICGA, CNV was correctly identified in about 60% of cases. Therefore, ICGA should be considered an indispensable diagnostic test to identify the presence, the type, and the location of occult CNV.

Infliximab for the treatment of posterior uveitis with retinal neovascularization in Behçet disease.

PURPOSE: To report a case of posterior uveitis with retinal neovascularization in a patient with Behçet disease treated with infliximab. METHODS: A 50-year-old man with a history of recurrent relapses of ocular inflammation despite immunosuppressive therapy developed retinal neovascularization near the optic disk. The patient was treated with infliximab and followed up for 12 months. RESULTS: Retinal neovascularization regressed 8 months after the first anti-tumor necrosis factor (TNF) treatment and with six infusions of infliximab. The ocular inflammation resolved almost completely. CONCLUSIONS: The result suggests that anti-TNF therapy may be effective in the treatment of retinal neovascularization caused by panuveitis in Behçet disease.

Infliximab for the treatment of posterior uveitis with retinal neovascularization in Behet disease.

PURPOSE: To report a case of posterior uveitis with retinal neovascularization in a patient with Behet disease treated with infliximab. METHODS: A 50-year-old man with a history of recurrent relapses of ocular inflammation despite immunosuppressive therapy developed retinal neovascularization near the optic disk. The patient was treated with infliximab and followed up for 12 months. RESULTS: Retinal neovascularization regressed 8 months after the first antitumor necrosis factor (TNF) treatment and with six infusions of infliximab. The ocular inflammation resolved almost completely. CONCLUSIONS: The result suggests that anti-TNF therapy may be effective in the treatment of retinal neovascularization caused by panuveitis in Behet disease. (Eur J Ophthalmol 2004; 14: #-8).

[ICG angiography and retinal pigment epithelial decompensation (CRSC and epitheliopathy)]. / ICG et décompensation de l'épithélium pigmenté rétinien (CRSC et épithéliopathies).

PURPOSE: To evaluate the prognosis of chronic central serous chorioretinopathy (CSC) and to assess whether certain clinical and angiographic features are associated with increased risk of vision loss. METHODS: All of the 51 patients with chronic CSC, who had received a baseline evaluation with fluorescein angiography (FA) and indocyanine green angiography (ICGA), during the last 5 years were retrospectively included in the study. RESULTS: The mean age was 49 years (range: 28-77 years). Sixteen out of 102 eyes (15.7%) of 14 patients lost at least 3 lines (0.3logMAR) after a mean follow-up of 34.7 months (range: 12-72 months). Logistic regression showed that CSC onset more than 7 years before inclusion (odds ratio: 4.3, p=0.024) and having areas of confluent RPE atrophy with FA at baseline (at least 2 disc diameters, odds ratio: 4.9,p=0.020) were independently associated with vision loss. Choroidal neovascularization was observed during follow-up in 4 eyes of 3 patients. CONCLUSION: Disease duration of more than 7 years and the presence of confluent RPE atrophy independently characterized CSC patients at higher risk for visual loss in our series.