Fluorescence lifetime imaging ophthalmoscopy and the influence of oral lutein/zeaxanthin supplementation on macular pigment (FLOS) - A pilot study.

BACKGROUND & AIMS: Oral lutein (L) and zeaxanthin (Z) supplementation enhances macular pigment optical density (MPOD) and plays a protective role in the development of age-related macular degeneration (AMD). Fluorescence lifetime imaging ophthalmoscopy (FLIO) is a novel in vivo retinal imaging method that has been shown to correlate to classical MPOD measurements and might contribute to a metabolic mapping of the retina in the future. Our aim was to show that oral supplementation of L and Z affects the FLIO signal in a positive way in patients with AMD. METHODS: This was a prospective, single center, open label cohort study. Patients with early and intermediate AMD received oral L and Z supplementation during three months, and were observed for another three months after therapy termination. All visits included measurements of clinical parameters, serum L and Z concentration, MPOD measurements using heterochromatic flicker photometry, dual wavelength autofluorescence imaging, and FLIO. Correlation analysis between FLIO and MPOD were performed. RESULTS: Twenty-one patients completed the follow up period. Serum L and Z concentrations significantly increased during supplementation (mean difference 244.8 ng/ml; 95% CI: 81.26-419.9, and 77.1 ng/ml; 95% CI: 5.3-52.0, respectively). Mean MPOD units significantly increased (mean difference 0.06; 95% CI: 0.02-0.09; at 0.5°, 202; 95% CI: 58-345; at 2°, 1033; 95% CI: 288-1668; at 9° of eccentricity, respectively) after three months of supplementation with macular xanthophylls, which included L and Z. Median FLIO lifetimes in the foveal center significantly decreased from 277.3 ps (interquartile range 230.2-339.1) to 261.0 ps (interquartile range 231.4-334.4, p = 0.027). All parameters returned to near-normal values after termination of the nutritional supplementation. A significant negative correlation was found between FLIO and MPOD (r2 = 0.57, p < 0.0001). CONCLUSIONS: FLIO is able to detect subtle changes in MPOD after L and Z supplementation in patients with early and intermediate AMD. Our findings confirm the previous described negative correlation between FLIO and MPOD. Macular xanthophylls seem to contribute to short foveal lifetimes. This study is registered at ClinicalTrials.gov (identifier number NCT04761341).

Combined cSLO-OCT imaging as a tool in preclinical ocular toxicity testing: A comparison to standard in-vivo and pathology methods.

INTRODUCTION: Confocal scanning laser ophthalmoscopy and optical coherence tomography (cSLO-OCT) became available for human and animal ophthalmic examinations in recent years. The purpose of this study was to evaluate lesion detection and localization with cSLO-OCT imaging in an experimental outer retinal toxicity model and to compare cSLO-OCT to standard examination methods (indirect ophthalmoscopy (IO), fundus photography (FP) and central section histopathology). METHODS: A test compound was orally administered to albino rats (n = 4) for four weeks (part A) and to albino (n = 2) and pigmented (n = 2) rats for eight weeks (part B). Control animals received vehicle only. Retinal changes were documented using cSLO-OCT, IO, FP, angiography and histopathology. Retinal thicknesses were compared between groups using a mixed effects model. RESULTS: All compound-treated animals developed progressive multifocal hyperreflective spot changes mostly confined to the retinal pigment epithelium. In study parts A and B, cSLO identified fundus lesions earlier than IO/FP in albino rats. In study part B, cSLO quantified fundus lesions more accurately than IO/FP in albino rats but no difference was seen in pigmented rats. Central section histopathology revealed no abnormalities in three out of four compound-treated animals in part B. Altogether, without cSLO-OCT, present fundus changes would have remained undetected in one of four compound-treated animals in both parts A and B. DISCUSSION: Integration of combined cSLO-OCT imaging into toxicology study design can improve toxicity study readouts and facilitate longitudinal examination of single animals at multiple time points, leading to a reduction of experimental animal numbers.

Reversal of cupping em glaucoma juvenil tratado com análogo de prostaglandina tópica / Reversal of cupping in juvenile glaucoma treated with topical prostaglandin analogue

Resumo A reversão da escavação é uma entidade rara que se refere à redução da escavação do disco óptico em resposta à diminuição sustentada dos níveis de pressão intra-ocular (PIO), em cerca de 25% da PIO basal. A ocorrência deste fenômeno apenas com o tratamento clínico é pouco relatada na literatura, Este estudo relata um caso de um paciente com glaucoma juvenil, que apresentou à gonioscopia ângulo aberto e tomografia de coerência óptica (OCT) com uma diminuição significativa na camada de fibras nervosas retinianas em ambos os olhos. Após um ano utilizando análogos de prostaglandina tópica e manutenção de níveis baixos de PIO, ocorreu diminuição da escavação do nervo óptico, que foi confirmada pelos padrões topográficos da OCT. O "reversal of cupping" é um sinal da diminuição da tensão ao nível da lâmina crivosa e está provavelmente associada a uma redução do risco para a progressão do glaucoma a longo prazo, sem melhora da função visual.

Abstract Reversal of cupping is a rare entity, characterized by the reduction of optical disc cupping in response to sustained decrease in intraocular pressure (IOP) levels by 25% of the basal IOP. The occurrence of this phenomenon with clinical treatment is rarely reported in the literature. This study reports a case of a patient with juvenile glaucoma with augmented cupping, significant decrease in the retinal nerve fiber layer in both eyes and altered topografic measures in optical coherence tomography (OCT). After one year using topical prostaglandin analog and keeping low IOP levels, a decrease in optic nerve cupping was detected in rethinography, confirmed by the improvement of OCT topographic measures. Reversal of cupping is a sign of decreased tension at the level of the lamina cribosa and is probably associated with a reduced risk for long-term progression of glaucoma without improvement of visual function.

LONG-TERM MULTIMODAL IMAGING OF OCULAR FINDINGS ASSOCIATED WITH THIAMINE-RESPONSIVE MEGALOBLASTIC ANEMIA.

PURPOSE: To report on 5-year multimodal imaging of ocular findings in a patient with thiamine-responsive megaloblastic anemia. METHODS: Observational case report. RESULTS: A 20-year-old-man with a history of thiamine-responsive megaloblastic anemia demonstrated a symmetric bull's eye maculopathy. Spectral domain optical coherence tomography revealed disruption of the parafoveal ellipsoid zone, fundus autofluorescence demonstrated foveal hypoautofluorescence, and full-field electroretinogram testing revealed a decreased photopic and scotopic response consistent with cone-rod dystrophy. His best-corrected visual acuity remained stable over 5 years at 20/50 in the right eye and 20/40 in the left eye, and visual field testing remained stable over time. CONCLUSION: Ocular manifestations in thiamine-responsive megaloblastic anemia are uncommon and variable. In this case, multimodal imaging and electroretinogram findings are consistent with cone-rod degeneration. The patient is taking daily thiamine supplementation, and visual acuity, funduscopic examination, spectral domain optical coherence tomography, and autofluorescence remained stable over a 5-year period.

Accuracy of computer-assisted vertical cup-to-disk ratio grading for glaucoma screening.

PURPOSE: Glaucoma screening can be performed by assessing the vertical-cup-to-disk ratio (VCDR) of the optic nerve head from fundus photography, but VCDR grading is inherently subjective. This study investigated whether computer software could improve the accuracy and repeatability of VCDR assessment. METHODS: In this cross-sectional diagnostic accuracy study, 5 ophthalmologists independently assessed the VCDR from a set of 200 optic disk images, with the median grade used as the reference standard for subsequent analyses. Eight non-ophthalmologists graded each image by two different methods: by visual inspection and with assistance from a custom-made publicly available software program. Agreement with the reference standard grade was assessed for each method by calculating the intraclass correlation coefficient (ICC), and the sensitivity and specificity determined relative to a median ophthalmologist grade of ≥0.7. RESULTS: VCDR grades ranged from 0.1 to 0.9 for visual assessment and from 0.1 to 1.0 for software-assisted grading, with a median grade of 0.4 for each. Agreement between each of the 8 graders and the reference standard was higher for visual inspection (median ICC 0.65, interquartile range 0.57 to 0.82) than for software-assisted grading (median ICC 0.59, IQR 0.44 to 0.71); P = 0.02, Wilcoxon signed-rank test). Visual inspection and software assistance had similar sensitivity and specificity for detecting glaucomatous cupping. CONCLUSION: The computer software used in this study did not improve the reproducibility or validity of VCDR grading from fundus photographs compared with simple visual inspection. More clinical experience was correlated with higher agreement with the ophthalmologist VCDR reference standard.

Determining Optic Nerve Cupping Using Optical Coherence Tomography (OCT) Versus a New Electronic Mobile Device.

PURPOSE: We present a new device that may aid in glaucoma screening. The vertical cup-to-disc ratio (CDR) obtained from a new electronic mobile device (EMD) was compared with that obtained from a spectral-domain optical coherence tomography. In addition, results from examiner's evaluations were compared with the results mentioned above. METHODS: A single-masked study was performed to evaluate the CDR results from 110 eyes from 110 subjects whose ages ranged between 18 and 60 years (39±13 y old), of whom 66 (60%) were female individuals. Vertical CDR was analyzed 5 times with each device in a single visit and evaluated by 3 different ophthalmologists. The Spearman correlation test and Bland-Altman analysis were used to evaluate the correlation and agreement between methods. RESULTS: The CDR average using spectral-domain optical coherence tomography was 0.47±0.04, whereas the CDR average using EMD was 0.42±0.02. The clinical evaluation resulted in an average of 0.34±0.27. The Spearman test showed a strong correlation between vertical CDR obtained with both devices (r=0.8319; P<0.0001) and between EMD and the examiners (r=0.7156; P>0.001). Bland-Altman analysis showed good agreement between both devices as well as between EMD and the examiners (95% limits of agreement from -0.20 to 0.10 and from -0.15 to 0.30, respectively). CONCLUSIONS: We present a low-cost, reliable EMD that may serve as an alternative to subjectively measuring vertical CDR in face-to-face consultations and hence increase the general public's access to glaucoma screening. This may be especially useful for patients who live in remote areas.

[Diagnostic Precision of the Confocal Scanning Laser Ophthalmoscopy in the Large Optic Disc with Physiological Excavation - a Long-Term Study]. / Diagnostische Zuverlässigkeit der konfokalen Scanning-Laser-Ophthalmoskopie bei großen Papillen mit physiologischer Exkavation ­ eine Langzeitstudie.

We repeatedly examined 17 subjects with presumed bilateral physiological excavation labeled as pathological and/or borderline via HRT to verify the diagnosis of physiological cupping or to monitor the long-term progression into normal tension glaucoma. PATIENTS AND METHODS: 17 Subjects with presumed bilateral physiological cupping and large optic discs were included in this long-term follow-up study. All subjects underwent regular detailed ophthalmologic examinations, including intraocular pressure measurement via Goldmann applanation tonometry (GAT), retinal nerve fiber layer imaging via optical coherence tonometry (OCT) and visual field testing and optic disc imaging using the HRT. Glaucomatous progression was identified using the HRT's tools (stereometric trend analysis [STA] and topographic change analysis [TCA]). RESULTS: In the initial examination, all 17 subjects were classified as "pathological", by the HRT's Moorfield's Regression Analysis (MRA). Over the observation period of 9.2 ± 5 years, only 1 of the 17 subjects showed an ensured conversion to normal tension glaucoma with glaucomatous visual field defects. The remaining 16 subjects show no visual field defects to date. STA showed significant changes in 3 subjects alone, in 1 subject TCA showed a significant change alone, and in 1 subject both analyses showed a progressive change. CONCLUSION: After 9 years of regular examinations, 16 of the 17 subjects that were classified as "pathological" using MRA showed no glaucomatous visual field defects. In 5 out of these 16 subjects, progressive changes of the optic disc could be recorded via HRT. Therefore, the diagnostic precision of the HRT measurements seems to be limited in patients with large discs and physiological cupping.

Diminuição da progressão da miopia com atropina 0, 025% / Decrease of myopia progression with 0. 025% atropine

Resumo Objetivo: Demonstrar a eficácia do uso do colírio de atropina 0,025% em crianças míopes, no Brasil, para a diminuição da progressão da miopia. Métodos: Realizou-se estudo prospectivo em 60 pacientes do Hospital Geral Universitário e Oftalmocenter Santa Rosa - Cuiabá - MT, com idades entre 6 e 12 anos, com equivalente esférico da refração entre -1,00 a -6,00 DE, refração cilíndrica < -1,00 DC e taxa de progressão anual de 0,50 DE (ou maior). Efetuou-se exame oftalmológico geral, topografia corneana e a medida do diâmetro anteroposterior do globo ocular (DAP). Os pacientes foram divididos em dois grupos: em que o Grupo 1 recebeu colírio de atropina 0,025%, todas as noites, e prescreveu-se a refração total com lentes com antirreflexo de multicamadas; e, no Grupo 2, somente a refração total. Nova avaliação foi realizada dois anos após. O teste T Student pareado foi utilizado para comparações das refrações, DAP e ceratometrias, medidas no exame inicial e no exame com 2 anos de seguimento. Resultados: Das 60 crianças, 30 eram do Grupo 1 com idade média de 8,21 ± 1,72 anos, e as do grupo controle com idade média de 8,17 ± 1,73 anos. Quatorze (46,66%) e 16 (53,33%) eram do sexo masculino nos Grupos 1 e 2, respectivamente. O Grupo 1 revelou menor progressão da miopia (Grupo 1: 0,43 ± 0,19D, Grupo 2: 1,24 ± 0,37D) e menor crescimento do DAP em relação ao grupo controle (Grupo 1: 0,19 ± 0,09mm, Grupo 2: 0,48 ± 0,12mm). Houve diferença estatisticamente significativa (P<0,05) entre o grupo tratado e o controle em relação à refração e ao crescimento DAP. A topografia não teve mudança estatisticamente significativa. Conclusão: A atropina em baixas concentrações foi eficaz em diminuir a progressão da miopia em 65% desta população estudada, por 2 anos. No entanto estudos com maior número de participantes e em diversas regiões do Brasil poderiam demonstrar melhor esse fato.

Abstract Purpose: To demonstrate the efficacy of 0.025% atropine eyedrops in myopic children in Brazil for decreasing myopia progression Methods: This was a prospective study with 60 children from Hospital Geral Universitário and Oftalmocenter Santa Rosa in Cuiabá, MT, Brazil, aged between 6 to 12 years, with spherical equivalent refractive error of -1.00 to -6.00 diopters (D) and astigmatism of -1.00 D or smaller. They underwent a complete ophthalmological examination, corneal topography and optical biometry. Children were assigned into two groups: group 1 used 0.025% atropine drop, once-nightly dosing, and it was prescribed total refraction in anti-reflective coating lens; and group 2 was prescribed just total refraction. A new evaluation was conducted 2 years after that. Paired student's t-test was used to compare refractions, axial length and keratometry which were measured in an initial exam and after a two-year follow-up. Results: Of the 60 children, the 30 in group 1 had an age mean and SD 8.21 +/- 1.72, and of the control group were 8.17 +/- 1.73 years. Fourteen (46,66%) and 16 (53,33%) were male, respectively. Myopic progression was significantly lower in group 1 (-0.43 +/- 0.19 D) than in group 2 (-1.24 +/- 0.37 D) and axial length increase was also significantly smaller in group 1(0.19 +/- 0.09 mm) than in group 2 (0.48 +/- 0.12 mm). There were no significant statistical differences regarding keratometry between groups. Conclusions: Low dose atropine eyedrops were effective in decreasing myopia progression in 65% of this population studied for 2 years. Furthermore, a larger scale randomized controlled study with longer follow-up seems warranted.

Combined trabeculotomy-trabeculectomy using the modified Safer Surgery System augmented with MMC: its long-term outcomes of glaucoma treatment in Asian children.

BACKGROUND: This study aimed to study the long-term surgical outcomes of combined trabeculotomy-trabeculectomy (CTT) using the modified Safer Surgery System in treating childhood glaucoma at a tertiary medical center in Taiwan. METHODS: Retrospective, consecutive, noncomparative case series. We retrospectively reviewed medical records of 42 pediatric patients (age 0-18 years) who had CTT performed on their 65 eyes using the modified Safer Surgery System. The study period spanned 18 years (from January 1, 1997, to December 31, 2014). We evaluated the outcome in terms of postoperative intraocular pressure (IOP), axial length growth, disc cupping reversal, and use of antiglaucoma medications. The surgical success was rated using the Kaplan-Meier survival analysis and based on the incidence of complications. RESULTS: The mean follow-up period was 85.05 ± 32.17 months (range 14-200). After operation, IOP dropped significantly from 35.76 ± 9.44 mmHg (mean ± SD) to 16.18 ± 7.20 mmHg together with a significant reversal of optic disc cupping. Similarly, the use of antiglaucoma medications was also significantly reduced in number from 1.26 ± 0.50 to 0.43 ± 0.70. Most of the axial lengths of the eyes measured at the last follow-up visit showed growths within the average ± 2 SDs in comparison with the healthy, age-matched population. After surgery, the qualified success rate was 90.77% at the end of the first year, 90.77% at the second year, 87.64% at the fifth year, 84.51% at the 10th year, and 81.38% at the 15th year. No serious intraoperative or postoperative complications were found. CONCLUSIONS: For Taiwanese children, the combined trabeculotomy-trabeculectomy using the modified Safer Surgery System offered an efficient and safe surgical option for treating glaucoma with long-term satisfactory control of IOP.

Pseudoxantoma elástico / Pseudoxanthoma elastic

Resumo O pseudoxantoma elástico é uma doença generalizada do tecido conjuntivo envolvendo a pele, olhos e sistema cardiovascular desencadeando a fragmentação e calcificação das fibras elásticas. Geralmente ocorre após a puberdade, as manifestações características são manchas pequenas, circunscritas, amareladas, localizadas no pescoço, axila e pregas inguinais. Estrias angioides na retina, tendência à hemorragia e insuficiência arterial são as complicações mais comuns. Esta doença pode ser herdada como autossômica dominante ou recessiva. O tratamento das manifestações oculares convencional é através da fototerapia a laser impedindo a ocorrência de hemorragias locais. Entretanto, novas abordagens terapêuticas estão sendo desenvolvidas como a utilização em longo prazo de drogas antiangiogênicas, as quais atuam inibindo a neovascularização ocular. Apesar de não ter ainda efetivamente substituído o tratamento original, pesquisas recentes já evidenciam benefícios da nova técnica. O objetivo deste estudo é relatar sobre o caso de uma paciente de 37 anos, portadora do pseudoxantoma elástico, com estrias angioides e hemorragia ocular, e o tratamento eficaz com a terapia antiangiogênica no ambulatório de oftalmologia em Nova Iguaçu, Rio de Janeiro.

Abstract The pseudoxanthoma elasticum is a generalized disease of the connective tissue involving the skin, eyes and cardiovascular system triggering the fragmentation and calcification of elastic fibers. Usually occurs after puberty, the manifestations characteristics are small spots, circumscribed, yellowish, located on the neck, axilla and inguinal folds. Angioid streaks in the retina, tendency to hemorrhage and arterial insufficiency are the most common complications. This disease can be inherited as autosomal dominant or recessive. The treatment of ocular manifestations is through the conventional phototherapy laser preventing the occurrence of local hemorrhages. However, new therapeutic approaches are being developed as the long-term use of drugs antiangiogenic, which act by inhibiting the ocular neovascularization. Despite not having yet effectively replaced the original treatment, recent research already show benefits of new technique. The objective of this study is to report on a case of a patient of 37 years, the carrier of the Pseudoxanthoma Elasticum, with angioid streaks and ocular hemorrhage, and the effective treatment with antiangiogenic therapy at the clinic of Ophthalmology in Nova Iguaçu, Rio de Janeiro.

Pattern noise (PANO): a new automated functional glaucoma test.

PURPOSE: To present a newly developed visual field device (pattern noise: PANO) designed to be sensitive to glaucoma defects, cost-effective, material-practical and easy to repair and therefore particularly suited for low-income countries, where glaucoma can be highly prevalent (e.g. sub-Saharan Africa). METHODS: This is primarily a descriptive paper, but it also includes a prospective matched case-control pilot study. Hardware, stimulus, target configuration, testing strategy and result sheet are described. The main outcome measure is the contrast level (range 2-64). Targets are composed of bright/dark pixels flickering with 18 Hz and have a size of 5°. Pixel size is approximated to the hill of vision. Average luminance of targets is constant and equals background luminance.The study was performed in the West Region in Cameroon. Twenty eyes of 20 newly presenting patients with glaucomatous optic disc cupping on funduscopy were compared with 20 eyes of 20 normal patients matched in age and laterality of eye. RESULTS: Mean age was 32.9 ± 18.8 years for glaucoma patients and 32.2 ± 15.6 years for healthy subjects. Mean contrast threshold was significantly higher in eyes with abnormal disc (16.2 ± 14.3 vs. 4.4 ± 0.8, P = 0.002). Correlation of mean contrast thresholds and cup-to-disc ratio was significant (r = 0.59; P = 0.006). Average examination time was significantly longer for glaucoma eyes compared to healthy eyes (8.2 vs. 6.1 min, P < 0.001), whereas error rate did not differ (4.8 ± 2.5% vs. 4.1 ± 1.8%, P = 0.33). CONCLUSION: PANO demonstrated visual field defects in patients with glaucomatous optic disc. Defects correlated significantly with glaucomatous optic nerve head morphological alterations. Healthy eyes obtained normal results. More studies are needed to establish PANO.

Effect of Dietary Supplementation With Lutein, Zeaxanthin, and ω-3 on Macular Pigment: A Randomized Clinical Trial.

Importance: Nutritional uptake of lutein, zeaxanthin, and ω-3 polyunsaturated fatty acids may increase macular pigment optical density (MPOD) and thereby protect against the development of age-related macular degeneration (AMD). Objectives: To estimate the efficiency of dietary supplementation containing lutein, zeaxanthin, ω-3 polyunsaturated fatty acids, and vitamins to increase the density of macular pigment in first-generation offspring of parents with neovascular AMD. Design, Setting, and Participants: This study was a randomized clinical trial (Lutein Influence on Macula of Persons Issued From AMD Parents [LIMPIA]) with a 6-month treatment period, followed by a 6-month follow-up period. Analyses were based on the intent-to-treat principle. The setting was 2 university hospitals in France (at Bordeaux and Dijon) from January 2011 (first participant first visit) to February 2013 (last participant last visit). The analysis was conducted from January to November 2016. Participants were 120 individuals free of any retinal ocular disease. They were first-generation offspring of parents with neovascular AMD. Interventions: Participants were randomized in a 1:1 ratio to receive either 2 daily dietary supplementation capsules or placebo for 6 months. Main Outcomes and Measures: The primary assessment criterion was the evolution of MPOD after 6 months of supplementation (value of both eligible eyes) measured using the modified MPD-Visucam 200 (Carl Zeiss Meditec) and the modified Heidelberg Retina Angiograph (Heidelberg Engineering) (HRA) at 0.98° eccentricity. The statistical analysis was adjusted for hospital and for risk factors. Results: Overall, 120 participants (60 in each group) were included, and 239 eyes were analyzed (119 in the lutein plus zeaxanthin [L + Z] group and 120 in the placebo group). Their mean (SD) age was 56.7 (6.6) years, and 71.7% (n = 86) were female. A statistically significant increase in plasma lutein and zeaxanthin was shown in the L + Z group after 3 months and 6 months of treatment compared with the placebo group. However, the difference between groups in the evolution of MPOD measured by HRA 0.98° eccentricity between 6 months and baseline was 0.036 (95% CI, -0.037 to 0.110) (P = .33). Conclusions and Relevance: Among first-generation offspring of parents with neovascular AMD in the LIMPIA trial, MPOD as measured with the modified HRA and the MPD-Visucam was not modified after 6 months of lutein and zeaxanthin dietary supplementation despite plasma levels showing continuous exposure to lutein and zeaxanthin. Further research is necessary to understand the mechanism of absorption and metabolism of these nutrients in the macula, the best way to measure MPOD, and the clinical benefit for the patients. Trial Registration: clinicaltrials.gov Identifier: NCT01269697.

Glaucoma.

Glaucoma is a heterogeneous group of diseases characterised by cupping of the optic nerve head and visual-field damage. It is the most frequent cause of irreversible blindness worldwide. Progression usually stops if the intraocular pressure is lowered by 30-50% from baseline. Its worldwide age-standardised prevalence in the population aged 40 years or older is about 3·5%. Chronic forms of glaucoma are painless and symptomatic visual-field defects occur late. Early detection by ophthalmological examination is mandatory. Risk factors for primary open-angle glaucoma-the most common form of glaucoma-include older age, elevated intraocular pressure, sub-Saharan African ethnic origin, positive family history, and high myopia. Older age, hyperopia, and east Asian ethnic origin are the main risk factors for primary angle-closure glaucoma. Glaucoma is diagnosed using ophthalmoscopy, tonometry, and perimetry. Treatment to lower intraocular pressure is based on topical drugs, laser therapy, and surgical intervention if other therapeutic modalities fail to prevent progression.

Electrophysiological assessment for early detection of retinal dysfunction in ß-thalassemia major patients.

PURPOSE: The purpose of this study was to assess the role of various diagnostic tests in early detection of retinal changes in ß-thalassemia major patients. METHODS: Thirty-eight visually asymptomatic ß-thalassemia major patients receiving regular blood transfusions and iron-chelation therapy with deferoxamine (group A, n = 13), deferasirox (group B, n = 11) or deferoxamine with deferiprone (group C, n = 14) and fourteen age- and sex- matched healthy individuals were included in the study. All participants underwent ophthalmoscopy, full-field electroretinography (ERG), visual evoked potentials (VEP), multifocal electroretinography (mfERG), fundus autofluorescence (FAF) imaging and optical coherence tomography (OCT) scans. RESULTS: Retinal pigment epithelium changes were present in two cases. Scotopic ERG demonstrated decreased a-wave amplitude in groups A, B and C (p = 0.03, p = 0.002 and p = 0.002, respectively) and decreased b-wave amplitude in groups B and C (p = 0.002 and p = 0.01, respectively) compared to controls. Photopic ERG showed delayed b-wave latency in groups A and C (p = 0.03 and p = 0.03, respectively) ERG maximal combined response and VEP response did not differ between groups. MfERG showed reduced retinal response density in ring 1 in groups A, B, C (p < 0.001, p < 0.001, p = 0.001, respectively) and ring 2 in group B (p = 0.02) and delayed latency in ring 5 in groups A and B (p = 0.04 and p = 0.04, respectively). Abnormal FAF images appeared in three cases and OCT abnormalities in one case, whereas no changes were observed in controls (p = 0.55 and p = 1.00, respectively). CONCLUSIONS: Full-field ERG and mfERG are more sensitive tools for detecting early retinal changes in ß-thalassemia patients compared with ophthalmoscopy, VEP, FAF imaging and OCT scans.

Episcleral brachytherapy of uveal melanoma: role of intraoperative echographic confirmation.

PURPOSE: To compare the rates of tumour recurrence following episcleral brachytherapy for uveal melanoma before and after implementation of intraoperative echographic confirmation of plaque placement. MATERIALS AND METHODS: All patients with primary single ciliary body or choroidal melanoma treated with iodine-125 or ruthenium-106 plaque brachytherapy between 1 January 2004 and 30 December 2013 were included. Exclusion criteria were patients with previous radiation treatment and patients who received adjuvant transpupillary thermotherapy. Since February 2007, intraoperative echographic confirmation was initiated to ensure that the plaque was centred on the tumour base and/or all tumour margins were covered by the plaque. RESULTS: 252 patients were included in the study. Local tumour control after primary brachytherapy was achieved in 242/252 (96.0%). Of the 10 patients with treatment failure, 8 patients had local recurrence and 2 patients had failure to response. With the incorporation of the intraoperative echographic confirmation for plaque positioning the treatment failure rate decreased from 9.3% (5/54 patients) to 1.5% (3/198 patients). Continuous and categorical univariable predictors of recurrence were analysed for statistical significance. The only statistically significant variable was the intraoperative echographic confirmation (HR: 0.16; p=0.032) for recurrence within the first 24 months. CONCLUSIONS: Intraoperative echographic confirmation of plaque placement during episcleral brachytherapy for choroidal melanoma reduces the risk of early local recurrence.

Evaluating outer segment length as a surrogate measure of peak foveal cone density.

Adaptive optics (AO) imaging tools enable direct visualization of the cone photoreceptor mosaic, which facilitates quantitative measurements such as cone density. However, in many individuals, low image quality or excessive eye movements precludes making such measures. As foveal cone specialization is associated with both increased density and outer segment (OS) elongation, we sought to examine whether OS length could be used as a surrogate measure of foveal cone density. The retinas of 43 subjects (23 normal and 20 albinism; aged 6-67years) were examined. Peak foveal cone density was measured using confocal adaptive optics scanning light ophthalmoscopy (AOSLO), and OS length was measured using optical coherence tomography (OCT) and longitudinal reflectivity profile-based approach. Peak cone density ranged from 29,200 to 214,000cones/mm2 (111,700±46,300cones/mm2); OS length ranged from 26.3 to 54.5µm (40.5±7.7µm). Density was significantly correlated with OS length in albinism (p<0.0001), but not normals (p=0.99). A cubic model of density as a function of OS length was created based on histology and optimized to fit the albinism data. The model includes triangular cone packing, a cylindrical OS with a fixed volume of 136.6µm3, and a ratio of OS to inner segment width that increased linearly with increasing OS length (R2=0.72). Normal subjects showed no apparent relationship between cone density and OS length. In the absence of adequate AOSLO imagery, OS length may be used to estimate cone density in patients with albinism. Whether this relationship exists in other patient populations with foveal hypoplasia (e.g., premature birth, aniridia, isolated foveal hypoplasia) remains to be seen.

Visual function and retinal vessel diameters during hyperthermia in man.

PURPOSE: To assess the effect of elevated core body temperature on temporal and spatial contrast sensitivity and retinal vessel diameters. METHODS: The study included 13 healthy volunteers aged 20-37 years. Core body temperature elevation (target +1.1°C) was induced by wrapping the participants in cling film, tinfoil and warming blankets. Subsequent cooling was achieved by undressing. Flicker sensitivity (critical flicker fusion frequency) was chosen to assess temporal resolution, while the Freiburg Vision Test was used to determine spatial contrast sensitivity at 1.5 cycles per degree. Scanning laser ophthalmoscopy was used to measure retinal trunk vessel diameters. Assessment was made at baseline, during hyperthermia and after cooling. RESULTS: The induction of a mean increase in core body temperature of 1.02°C was associated with a 7.15-mmHg mean reduction in systolic blood pressure (p < 0.01), a 10.6-mmHg mean reduction in diastolic blood pressure (p < 0.01), a mean increase in pulse rate of 36.3 bpm (p < 0.0001), a 2.66% improvement in flicker sensitivity (CI95 1.37-3.94, p < 0.001), a 2.80% increase in retinal artery diameters (CI95 1.09-4.51, p < 0.01) and a 2.95% increase in retinal vein diameters (CI95 0.96-4.94, p < 0.01). There was no detectable effect of temperature on spatial contrast sensitivity. All ocular test parameters returned to baseline levels after cooling. CONCLUSION: Increased core body temperature was accompanied by improved temporal visual resolution and retinal trunk vessel dilation. The results suggest that hyperthermia is associated with enhanced retinal function and increased retinal metabolism.

[The efficacy of large spot indirect ophthalmoscopy laser alone or combined with systemic chemotherapy in retinoblastoma therapy].

Objective: To evaluate the efficacy of large spot indirect ophthalmoscopy laser alone or combined with systemic chemotherapy in the treatment of early and middle stage retinoblastoma. Methods: Retrospective series case study. Clinical data of 21 patients (22 eyes) who were diagnosed as retinoblastoma (RB) in Peking University People's Hospital from March 2009 to August 2014 were collected. Medical and family history, ocular ultrasound, orbital and cranial MRI or CT examination of RB Children were detailed recorded. Ocular examination and laser treatment were performed under general anesthesia, once every 3-4 weeks until the tumor was under control. The observation period was at least 3 months after the last treatment. The ocular examination included intraocular pressure measurement, anterior segment and fundus examination and the fundus photography with Retcam. Laser therapeutic instrument was large spot indirect ophthalmoscopy laser of 810nm wavelength. Results: Of the 21 children, 16 were male and 5 were female. The range of age was 3 to 82 months averaged 17.3 months. Among 22 eyes, four with small tumor, eight with medium tumor, and ten with large tumor. Two eyes underwent laser treatment only and 20 eyes underwent laser treatment combined with systemic chemotherapy. During the average observation period of 33.9 months, 15 tumors were treated successfully, but 7 failed. The total success rate was 68.2%. The number and success rate of small, medium and large tumor eyes were 4 (100%), 5 (62.5%) and 5 (50%), respectively. There was one case of tumor brain metastases, and the classification of contralateral eye of the child was E phase. COMPLICATIONS: Iris burns happened in one eye, obvious vitreous proliferation in one eye and mild vitreous hemorrhage occurred in two eyes, which did not affect the treatment of laser. However, obvious tumor hemorrhage happened in two eyes and affected laser therapy. There was no complicated cataract, iatrogenic retinal hole and tumor intravitreal implant caused by laser blasting effect. Conclusions: Indirect ophthalmoscope laser in 810-nm diode laser with large-spot alone or combined with systemic chemotherapy may be effective treatment for retinoblastoma in earlier than stage C of international classification. It is suitable for large and multiple retinoblastoma.(Chin J Ophthalmol, 2016, 52: 745-748).

Clinical outcome and regression patterns of retinoblastoma treated with systemic chemoreduction and focal therapy: A prospective study.

PURPOSE: To prospectively study the clinical outcome and regression patterns of early retinoblastoma (Groups A and B) after systemic chemotherapy and focal consolidation in Indian children. MATERIALS AND METHODS: Group A eyes were treated with focal therapy (transpupillary thermotherapy/cryotherapy) and Group B with systemic chemoreduction and focal therapy. Outcome measures were efficacy and safety of treatment, risk factors for treatment failure, regression patterns, and factors predictive of regression patterns. RESULTS: Of 119 eyes (216 tumors), 14 (11.8%) were Group A and 105 (88.2%) were Group B eyes. The mean follow-up was 22.6 months. Tumor control was achieved in 111/119 eyes (93.3% overall, 100% Group A, 92.4% Group B). Eight Group B eyes (6.7%) had treatment failure. No serious systemic side-effects were noted. Risk factors for failure included larger tumors (P = 0.001) and proximity to posterior pole (P = 0.014). Regression patterns were Type 4 (50.2%), Type 3 (31.7%), Type 1 (11.1%), and Type 2 (7%). Factors predictive of Type 4 regression were smaller tumors, anterior location, younger age; Type 3 regression was associated with larger tumors, macular location, and older age. CONCLUSIONS: Systemic chemoreduction and focal therapy provided effective tumor control in Indian children. Factors predictive of regression patterns included age, tumor size and its location, and the modality of treatment.

Green tea catechins are potent anti-oxidants that ameliorate sodium iodate-induced retinal degeneration in rats.

Green tea extracts exhibit anti-oxidative and anti-inflammatory actions in different disease conditions. We hypothesized that green tea extract and its catechin constituents ameliorate sodium iodate-induced retinal degeneration in rats by counteracting oxidative stress. In this study, adult Sprague-Dawley rats were intravenously injected with a single dose of sodium iodate. Green tea extract (GTE; Theaphenon-E) or combinations of its catechin constituents, including (-)-epigallocatechin gallate (EGCG), were administered intra-gastrically before injection. Live imaging analysis using confocal scanning laser ophthalmoscopy and spectral-domain optical coherence tomography showed a progressive increase of degenerating profile across the retinal surface and decrease in thickness of outer nuclear layer (ONL) at Day-14 of post-injection. These lesions were significantly ameliorated by Theaphenon-E and catechin combinations with EGCG. Catechins with exclusion of EGCG did not show obvious protective effect. Histological analyses confirmed that Theaphenon-E and catechins containing EGCG protect the retina by reducing ONL disruption. Retinal protective effects were associated with reduced expression of superoxide dismutase, glutathione peroxidase and caspase-3, and suppression of 8-iso-Prostaglandin F2α generation in the retina. In summary, GTE and its catechin constituents are potent anti-oxidants that offer neuroprotection to the outer retinal degeneration after sodium iodate insult, among which EGCG is the most active constituent.