Ocular alterations, molecular findings, and three novel pathological mutations in a series of NF2 patients.

PURPOSE: To evaluate ophthalmological and molecular findings in eight patients with a clinical diagnosis of neurofibromatosis type 2 (NF2). New pathological mutations are described and variability in the ophthalmic phenotype and NF2 allelic heterogeneity are discussed. METHODS: Eye examination was performed in eight NF2 patients, and it included the measurement of the visual acuity, biomicroscopy, dilated fundus examination, color fundus photography, infrared photography, and spectral domain optical coherence tomography (SD-OCT). Molecular analysis was performed with whole-exome sequencing using DNA derived from peripheral blood mononuclear cells from each individual. RESULTS: Ophthalmological features were present in all patients, ranging from subtle retinal alterations identified only using SD-OCT to severe ocular damage present at birth. Six mutations were observed: two patients with stop codon mutation as shown on table 1 and result section, three patients with frameshift mutation as shown on table 1 and result section. Three novel mutations were found among them. CONCLUSIONS: It is a descriptive study of a rare disease, with poor previous literature. Clinical and genetic data are shown, reviving the need to further studies to clarify the genotype-phenotype correlations in NF2.

Quantitative analysis of external limiting membrane, ellipsoid zone and interdigitation zone defects in patients with macular holes.

PURPOSE: To investigate the correlation between the length of external limiting membrane (ELM), ellipsoid zone (EZ) and interdigitation zone (IZ) defects and visual prognosis in patients undergoing macular hole (MH) surgery, using spectral-domain optical coherence tomography (SD-OCT). METHODS: This is a retrospective, consecutive, observational case series study. Fifty-two eyes of 52 patients with primary MH were evaluated. A quantitative analysis of ELM, EZ and IZ defects was performed preoperatively and at 3 and 6 months postoperatively using SD-OCT. The correlation between pre- and postoperative ELM, EZ and IZ defects and the best-corrected visual acuity (BCVA) was investigated. RESULTS: The lengths of ELM, EZ and IZ defects correlated significantly with BCVA in each study period (P < 0.001). Preoperative measures of these band defects were also associated with visual outcomes 3 and 6 months after surgery (P < 0.05). Considering all preoperative parameters, the length of the ELM defect was the factor most strongly correlated with BCVA at 6 months (ß = 0.643, P < 0.012). The integrity of the ELM was the only factor significantly associated with BCVA at 6 months (ß = 0.427; P = 0.004). CONCLUSIONS: The preoperative length of the ELM defect is the strongest predictor of visual acuity after MH surgery. Postoperative integrity of the ELM is significantly associated with visual restoration after surgical treatment of MH.

Influence of Vitreomacular Adhesion on Anti-Vascular Endothelial Growth Factor Treatment for Neovascular Age-Related Macular Degeneration.

PURPOSE: To investigate the effect of vitreomacular adhesion (VMA) on the outcome of antiangiogenic treatment for neovascular age-related macular degeneration (AMD). METHODS: Ninety-nine eyes of 83 patients were used in our cohort study. We prospectively evaluated best corrected visual acuity (BCVA) and central retinal thickness (CRT) in patients with neovascular AMD at baseline and 1, 2, 3, 6, and 12 months after treatment with anti-vascular endothelial growth factor (anti-VEGF) agents. All patients were stratified by spectral domain optical coherence tomography into 2 groups (i.e., VMA[+] and VMA[-]) according to the presence or absence of VMA, and the response to treatment was evaluated. RESULTS: Fifty-four eyes (54.5%) were included in the VMA(-) group and 45 eyes (45.5%) comprised the VMA(+) group. In paired comparisons of mean BCVA between baseline and each follow-up visit (1, 2, 3, 6, and 12 months), the VMA(-) group showed statistically significant improvement at 1, 2, and 3 months compared to baseline, and BCVA significantly improved only at 3 months in the VMA(+) group. For both groups, paired comparisons of CRT showed a statistically significant decrease when data obtained at 1, 2, 3, 6, and 12 months were compared to baseline values (p < 0.05). CONCLUSIONS: Posterior VMA is associated with a worse short-term outcome in patients with neovascular AMD treated with anti-VEGF agents.

VEGF gene polymorphism and response to intravitreal ranibizumab in neovascular age-related macular degeneration.

BACKGROUND/AIMS: To investigate the association between VEGF gene polymorphism and response to ranibizumab in neovascular age-related macular degeneration (AMD). METHODS: A total of 92 patients were genotyped for the VEGF rs1413711 single nucleotide polymorphism. Patients with neovascular AMD initially received 3 monthly ranibizumab intravitreal injections and were retreated as needed. Visual acuity (VA) and central retinal thickness (CRT) were measured before and 1, 3, 6 and 12 months after treatment. RESULTS: For patients with TT and CT genotypes, paired comparisons of mean VA showed improvement when the data obtained at all visits were compared with baseline values, in contrast to patients with the CC genotype. CRT statistically improved at all visits for all genotypes. CONCLUSION: Patients with the CC genotype showed poorer long-term functional and anatomical response to anti-VEGF therapy.

Vancomycin-associated hemorrhagic occlusive retinal vasculitis masquerading as central retinal vein occlusion.

A 69-year-old female was referred with sudden unilateral painless decreased vision that began 2 days after uncomplicated cataract surgery in the left eye. Visual acuity was hand motion and biomicroscopy showed a mild anterior chamber reaction, no hypopyon, and an intraocular lens that had been placed within the capsular bag. A dilated fundus examination revealed optic disk edema, widespread deep and superficial intraretinal hemorrhages, retinal ischemia, and macular edema. A cardiological evaluation was normal and thrombophilia tests were negative. After surgery, prophylactic vancomycin (1mg/0.1ml) had been injected intracamerally. The patient was diagnosed with hemorrhagic occlusive retinal vasculitis likely secondary to vancomycin hypersensitivity. Recognition of this entity is important to ensure early treatment and the use of intracameral vancomycin in the fellow eye should be avoided after cataract surgery.

Homozygosity for the +674C>T polymorphism on VEGF gene is associated with age-related macular degeneration in a Brazilian cohort.

PURPOSE: To investigate the association between VEGF gene polymorphism and age-related macular degeneration (AMD) in a Brazilian cohort. METHODS: We examined 160 affected individuals and 140 sex- and age-matched controls recruited at the Vision Institute and the Retina Department, São Geraldo Hospital, Minas Gerais Federal University, Brazil, between 2007 and 2011. Genotyping for the VEGF rs1413711 single nucleotide polymorphism (SNP) (+674C>T) was performed. The incidence rate ratios and 95% confidence interval (CI) for AMD for this genotype was calculated. The odds ratio (OR) was also assessed by using logistic regression, controlling for CFH and LOC387715 risk genotype. RESULTS: We observed a prevalence of homozygosity (TT genotype) of 18.1% for rs1413711 among AMD cases compared with 5.8% among controls (P < 0.002). The ORs for this polymorphism were 3.6 (95%CI 1.6-8.2) for homozygous subjects and 1.5 (95%CI 1.1-2.1, P < 0.01) if the subject had at least one risk allele. When we studied separately exudative and dry AMD groups, this polymorphism was statistically significant for both groups. Controlling for CFH and LOC387715 risk genotype the OR was 3.0 for VEGF homozygous, and the OR increases if the patient is homozygous for the three genes. CONCLUSION: The present data suggests that VEGF TT genotype is associated with AMD among Brazilian patients.

Decisive role of histopathology of lens capsule in the diagnosis of chronic fungal postoperative endophthalmitis.

We report three cases of refractory chronic endophthalmitis after cataract surgery presenting to a referral center, and with repeated negative cultures. Initial treatment consisted of intravitreal and systemic antibiotics, with partial improvement. After subsequent worsening, pars plana vitrectomy, intraocular lens explantation and en bloc capsulectomy were performed. Histopathological examination revealed multiple filamentous fungal structures, sequestered between anterior/posterior lens capsule in all cases. Chronic postoperative fungal endophthalmitis may manifest with negative cultures possibly associated with sequestration of the microorganism into the capsular bag. Careful histopathological examination of lens capsule in these cases may be essential for a definite diagnosis.

Humanistic and Economic Burden of Blindness Associated with Retinal Disorders in a Brazilian Sample: A Cross-Sectional Study.

INTRODUCTION: Vision impairment and blindness have been significantly associated with high medical care expenditures, decrease in health utility, and loss or reduction of productivity. The objective of this study was to assess the humanistic and economic burden of blindness in a Brazilian sample from a societal perspective. METHODS: Cross-sectional, observational, and multicenter study enrolling individuals with blindness (defined as the best corrected visual acuity less than 6/60 in the better-seeing eye) caused by retinal disorders. Data collection was performed between December 2012 and December 2014 through face-to-face interview using a structured questionnaire and three standardized patient-reported outcomes instruments. Direct costs were estimated by multiplying the amount of resources used (12-month recall period) by the corresponding unit cost. Productivity losses were measured using the human capital method. All data were collected in Brazilian real (BRL) and converted to United States dollar (USD), using the exchange rate of 1 USD = 3.0415 BRL (May 7, 2015). RESULTS: A total of 146 subjects from 17 research sites were included with a mean age of 68 (SD = 14.8) years and equal gender distribution. Blindness negatively affected both general and vision-specific health-related quality of life. One-half of patients presented some level of anxiety and depression; of these, about 50% with moderate or severe symptoms. Around one-third of subjects (34.2%) reported at least one fall in the previous 12 months due to vision impairment; of these subjects, 14% reported fractures. Emergency room visits and hospitalization were reported by around 25% and 5% of subjects, respectively. The short-term costs (annual costs) of severe vision impairment or blindness for the studied subjects was USD 128,389.09 (USD 879.37 per person). Total medical direct costs summed USD 116,182.00 (USD 795.77 per person), 61.7% of which was due to outpatient visits (with physicians and other healthcare professionals). The long-term costs (lifetime productivity loss) totalized USD 1,962,599.50 (USD 13,442.47 per person). CONCLUSION: This study demonstrated that blindness imposes both humanistic and economic burden for individuals and for Brazilian society. It also pointed out that there is room to improve blindness management, especially for the poorest people, including health education for individuals, availability of services, and reduction of barriers to patients' access to healthcare assistance. This was a good starting point; however, further research is needed.

Vancomycin-associated hemorrhagic occlusive retinal vasculitis masquerading as central retinal vein occlusion / Vasculite hemorrágica oclusiva da retina associada à vancomicina (HORV) mascarada como oclusão da veia central da retina

ABSTRACT A 69-year-old female was referred with sudden unilateral painless decreased vision that began 2 days after uncomplicated cataract surgery in the left eye. Visual acuity was hand motion and biomicroscopy showed a mild anterior chamber reaction, no hypopyon, and an intraocular lens that had been placed within the capsular bag. A dilated fundus examination revealed optic disk edema, widespread deep and superficial intraretinal hemorrhages, retinal ischemia, and macular edema. A cardiological evaluation was normal and thrombophilia tests were negative. After surgery, prophylactic vancomycin (1mg/0.1ml) had been injected intracamerally. The patient was diagnosed with hemorrhagic occlusive retinal vasculitis likely secondary to vancomycin hypersensitivity. Recognition of this entity is important to ensure early treatment and the use of intracameral vancomycin in the fellow eye should be avoided after cataract surgery.

RESUMO Esse caso se refere a uma paciente de 69 anos, sexo feminino, com relato de baixa acuidade visual súbita e indolor no olho esquerdo, de início 2 dias após cirurgia de catarata sem complicações. A acuidade visual era de movimento de mãos e a biomicroscopia mostrou reação de câmara anterior moderada, sem hipópio, e lente intraocular posicionada dentro do saco capsular. A fundoscopia evidenciou edema de disco óptico, hemorragias difusas intrarretinianas superficiais e profundas, isquemia retiniana e edema macular. A avaliação cardiológica foi normal e os testes para trombofilia foram negativos. Ao final da cirurgia foi injetado antibioticoprofilaxia com vancomicina (1mg/0,1ml) na câmara anterior. A paciente foi diagnosticada com vasculite hemorrágica oclusiva da retina secundária à hipersensibilidade a vancomicina. O reconhecimento dessa entidade é importante para o tratamento precoce e para evitar o uso de vancomicina intracameral em caso de cirurgia de catarata no olho contralateral.

Macular edema associated with gyrate atrophy managed with intravitreal triamcinolone: a case report.

PURPOSE: To describe the use of 4 mg intravitreal triamcinolone acetonide (IVTA) for gyrate atrophy-related macular edema (ME) and to report anatomic and functional outcomes, during a nine-month period. CASE REPORT: A 27-year-old female complained of decreased vision since diagnosis of gyrate athrophy (GA), six years before admission. At presentation visual acuity was 20/100 in OD and 20/80 in OS. Ophthalmological examination disclosed significant cataract in OD, pseudophakia in OS and typical GA findings. Fluorescein angiography (FA) disclosed ME that was confirmed by optical coherence tomography (OCT), which also showed subfoveal fluid. OS was treated with a 4-mg IVTA injection. One month later, vision improved to 20/50+1 and foveal thickness decreased, with less leakage in FA. This picture was maintained up to six months, when there was recurrence of ME to a level similar to the baseline. At nine months, visual acuity dropped to 20/80, and ME was maintained, with remodeling in macular profile. CONCLUSION: There is a transient therapeutic effect with 4-mg IVTA injection for GA-related ME. After drug clearance, edema recurs, with return of visual acuity to pretreatment level.

The white dot syndromes.

Several entities must be considered when a patient presents with a white dot syndrome. In most cases these can be distinguished from one another based on the appearance or distribution of the lesions, the clinical course, or patient variables such as age, sex, laterality, and functional and image examinations. In this paper we review the distinctive and shared features of the white dot syndromes, highlighting the clinical findings, diagnostic test results, proposed etiologies, treatment, and prognosis.

[Evaluation of macular perimetry in patients with age-related macular degeneration using the scanning laser ophthalmoscope]. / Avaliação da perimetria macular em pacientes com degeneração macular relacionada à idade por meio do oftalmoscópio de rastreamento a laser.

PURPOSES: To evaluate the correlation between anatomical changes (hard druses, soft druses, hyperpigmentation, new vessels, detachment of retinal pigment epithelium, hypopigmentation and chorioretinal atrophy) and light sensitivity in patients with age-related macular degeneration (ARMD); analyze macular sensitivity in areas with no anatomical lesions in patients with ARMD and compared them to the control group in order to detect if there was any functional lesion in areas with no anatomical changes. METHODS: A cross-sectional, comparative, descriptive and analytic study was performed. The case group consisted of 31 subjects with ARMD aged between 51 and 88 years. The control group consisted of 31 "healthy" subjects, without ARMD aged between 61 and 80 years. The groups were matched for gender and age. We performed static macular perimetry, red-red, using a scanning laser ophthalmoscope (SLO). Results of macular perimetry were correlated with the anatomic lesion identified in the same site by infrared laser and color photographs. RESULTS: Areas with new vessels or atrophy showed a significantly different sensitivity in relation to areas without anatomical lesions in patients with ARMD. There was significant functional loss in areas with no anatomical lesions in patients with ARMD in relation to the control group. CONCLUSIONS: Areas with new vessels or atrophy could be distinct factors for worsening of the localized macular sensitivity. There might be functional loss even in areas with no apparent anatomical changes in ARMD patients.

[Age-related macular degeneration: new perspectives]. / Degeneração macular relacionada à idade: novas perspectivas.

Age-related macular degeneration (ARMD) is a major source of legal blindness in individuals older than 50 years. Even though recent reports suggest that genetics plays an important role, its pathogenesis remains puzzling and the risk factors for its occurrence are not completely established. Vitamin and mineral supplementation reduced the risk of development of choroidal neovascularization (CNV) or progression to the most advanced stages of age-related macular degeneration. Photodynamic therapy (PDT) and antiangiogenic therapy have proved to be very useful for the treatment of choroidal neovascularization associated to age-related macular degeneration, by reducing the risk of vision loss and, occasionally, by a temporary improvement of vision. Only a small subset of patients may benefit from other treatment modalities, such as laser photocoagulation, surgical removal of choroidal neovascularization and transpupillary thermotherapy (TTT). Strategies to control and treat age-related macular degeneration may progress quickly as more is learned about its pathophysiology and the molecular events that contribute to the disease expression.

[Clinical characteristics and incidence of infectious and non-infectious endophthalmitis after intravitreous injection of triamcinolone acetonide]. / Avaliação clínica e incidência de endoftalmite infecciosa e não-infecciosa após injeção intravítrea de acetonida de triancinolona.

PURPOSE: To report the incidence of infectious and noninfectious endophthalmitis after intravitreal injection of 4 mg of triamcinolone acetonide (Kenalog - 40 mg/ml; 0.1 ml) and to evaluate distinguishing characteristics that may assist the clinician in differentiating these entities. DESIGN: Observational nonconcurrent prospective study. METHODS: Charts of 121 patients (154 injections) who consecutively underwent intravitreal injection of triamcinolone acetonide to treat various chorioretinal diseases were evaluated. All procedures were performed in an operating room with careful antiseptic protocol. RESULTS: Two eyes (1.29%/injection and 1.65%/patient) presented a noninfectious endophthalmitis characterized by decreased vision, hyperemia, hypopyon and vitreous inflammatory reaction, on the first day after the injection. These eyes were treated with topical and subconjunctival corticosteroids with complete resolution of the inflammatory reaction. CONCLUSION: In the present case series, no case of infectious endophthalmitis occurred. Despite being relatively rare, noninfectious endophthalmitis can be associated with intravitreal injection of triamcinolone simulating an infectious endophthalmitis. In selected cases, the differential diagnosis can be made solely by clinical evaluation.

Ultrasound biomicroscopy in the comparison of the anterior segment morphometry before and after pars plana vitrectomy.

PURPOSE: To determine if pars plana vitrectomy induces long-term changes in the anterior segment anatomy by means of ultrasound biomicroscopy. METHODS: A prospective case series study was undertaken of consecutive patients referred to a tertiary eye care centre for pars plana vitrectomy as the only procedure. Twenty eyes of 20 patients undergoing pars plana vitrectomy alone were studied by ultrasound biomicroscopy. Silicone oil or scleral buckle was not used in any of the included cases. The following morphometric parameters were compared before and after 3 months of surgery: anterior chamber depth, angle-opening distance at 500 microm from the scleral spur, trabecular-ciliary process distance, ciliary body thickness at 1, 2 and 3 millimeters from the scleral spur and measurement of the supraciliary space thickness, when fluid was detected. RESULTS: No statistically significant differences were found between the preoperative and the postoperative morphometric parameters. CONCLUSION: Uncomplicated pars plana vitrectomy does not induce any long-term change on anterior segment morphometry. Based on these findings, the normal long-term pattern to be expected after pars plana vitrectomy is the conservation of the preoperative morphometry.

Spectral-Domain Optical Coherence Tomography Findings in Neurofibromatosis Type 2.

PURPOSE: Neurofibromatosis type 2 (NF2) is an autosomal-dominant disease, characterized by bilateral vestibular schwannomas, multiple central nervous system (CNS) tumors, skin tumors, and juvenile cataract. The present study assessed retinal abnormalities using spectral-domain optical coherence tomography (SD-OCT) in a case series of NF2 patients. METHODS: Nine NF2 patients from the neurofibromatosis outpatient reference center of the Federal University of Minas Gerais, in Brazil, were submitted to a complete anamnesis and a detailed ophthalmic evaluation, including SD-OCT, to detect retinal lesions. RESULTS: Of the nine NF2 patients evaluated, five had an early onset (<20 years) of NF2, and four patients had a late onset (>20 years) of symptoms. SD-OCT scans revealed retinal abnormalities in every patient with early onset (EOS) and in two patients with late onset (LOS) of the disease. In the EOS group, SD-OCT scans revealed flame-shaped epiretinal membranes (ERM) with peculiar characteristics in four eyes of three patients. Two patients had fine undulations of the inner retinal surface with a subtle ERM. Retinal hamartomas were present in four eyes of three patients with EOS; in two eyes, they were subclinical and were detected only by SD-OCT scans. In two patients with LOS and one patient with EOS, SD-OCT scans revealed retinal tufts of a nerve fiber layer. CONCLUSIONS: SD-OCT revealed ERM in most patients with NF2, therefore it may be a valuable exam for evaluating NF2 patients. Epiretinal membranes in NF2 has unique features, distinguishing it from idiopathic ERM or membranes associated with other diseases. We suggest that flame-shaped ERM seems to be specific for NF2 and that ERM can be considered as an important diagnostic sign of NF2.

[Macular infarction after intravitreal injection of amikacin: case report]. / Maculopatia isquêmica após injeção intravítrea de amicacina: relato de caso.

The authors report a case of a patient who underwent cataract surgery with implantation of a posterior chamber intraocular lens and presented endophthalmitis on the second postoperative day. She was treated with intravitreal injection of amikacin, vancomycin and dexamethasone. After resolution of the infection the patient presented macular infarction and important loss of visual acuity due to amikacin toxicity.

Causes of visual impairment in children seen at a university-based hospital low vision service in Brazil.

PURPOSE: To evaluate the epidemiologic characteristics of patients 0-7 years of age with visual impairment registered at a university hospital low vision service in Brazil. METHODS: The medical records of visually impaired patients were retrospectively reviewed for sociodemographic characteristics and ocular and associated deficiencies. In addition to biographical information, the following data were collected: ocular disorders, diagnosis, affected anatomic region, etiology, and avoidable or unavoidable causes. RESULTS: A total of 229 patients were included, 65% of whom were referred from rural health centers. The mean age at first appointment was 39.4 months. Associated nonophthalmic disorders were present in 47% of patients. The most prevalent disorders were congenital cataract (14%), toxoplasmosis (14%), and congenital glaucoma (13%). The most commonly affected anatomic regions were the retina (18%) and lens (15%); 33% had a normal-appearing globe. Using World Health Organization classifications, the most prevalent underlying etiologies were undetermined (43%), perinatal/neonatal factors (22%), and intrauterine factors (20%). Avoidable causes were found in 64% of the children. CONCLUSIONS: The three leading causes of infant blindness in our patient cohort were congenital cataract, toxoplasmosis, and congenital glaucoma. The most commonly affected anatomic regions were retina, lens, and normal-appearing globe. The percentage of avoidable causes of impairment was high and the mean age at first appointment was late.

CFH Y402H polymorphism and response to intravitreal ranibizumab in Brazilian patients with neovascular age-related macular degeneration.

OBJECTIVE: To investigate the association between CFH gene polymorphism and response to ranibizumab in Brazilian patients with neovascular age-related macular degeneration (AMD). METHODS: 95 patients were genotyped for the CFH rs1061170 (Y402H) single nucleotide polymorphism. Patients with neovascular AMD initially received intravitreal ranibizumab injections for three months and were retreated as needed. Visual acuity (VA) and central retinal thickness (CRT) were measured before treatment and at 1, 3, 6, and 12 months post-treatment. RESULTS: For patients with the TT and TC genotypes, paired comparisons of VA showed a statistically significant improvement when the data obtained at all visits were compared with baseline. Patients homozygous for the risk genotype (CC) did not show a statistically significant improvement when VA obtained at visits 1, 3, 6 and 12 were compared with baseline. For all genotypes, paired comparisons of CRT showed a statistically significant improvement when the data obtained at visits 1, 3, 6 and 12 were compared with baseline. CONCLUSION: Patients with the CC genotype showed poorer long-term functional response to intravitreal ranibizumab.