Choriocapillaris and choroidal thickness in all Leber hereditary optic neuropathy stages using swept source technology.

PURPOSE: The role of the choroid in Leber hereditary optic neuropathy (LHON) remains unclear. The literature is scarce, with conflicting results and lacks axial length measurements. Therefore, we aimed to analyse the choriocapillaris (CC) vessel density (VD) and choroidal thickness (ChT) in all stages of LHON using swept source (SS) technology and considering the possible influence of axial length on choroidal parameters. METHODS: This was a prospective cross-sectional observational study. A total of 119 eyes of 60 patients with molecularly confirmed LHON across all stages and 120 eyes of 60 control participants were included. We obtained the CC VD using optical coherence tomography angiography maps centred on the fovea. ChT was measured from the Bruch's membrane to the choroid-sclera interface in the macular and peripapillary regions. RESULTS: The CC VD was not significantly affected in any sector or average, except for a slight change in the superior region of chronic eyes (52.08 ± 1.62% vs. 53.50 ± 2.29%, p = 0.002). ChT demonstrated a trend towards decreased values in asymptomatic eyes and increased values in the symptomatic stages that failed to reach statistical significance in sectors corresponding to the papillomacular bundle except for the macular nasal inner sector of chronic eyes (281.10 ± 67.12 µm vs. 252.08 ± 70.55 µm, p = 0.045). No significant correlations were observed between visual acuity and CC VD or ChT. CONCLUSION: The CC VD remained stable across the LHON stages. Choroidal vasculature does not appear to play a role in LHON pathophysiology. Further research is needed on ChT as a potential biomarker of LHON.

The Effect of Oral Citicoline and Docosahexaenoic Acid on the Visual Field of Patients with Glaucoma: A Randomized Trial.

The role of nutraceuticals in the treatment of glaucoma remains controversial. The aim of this study was to evaluate the effect of citicoline, vitamin C, and docosahexaenoic acid (DHA) in patients with glaucoma. METHODS: This was a prospective, randomized study. Patients with glaucoma were randomized to one of four groups and treated for 3 months with vitamin C, DHA, citicoline, or a combination of DHA and citicoline. We conducted a complete ophthalmic examination and visual fields each month and calculated the slopes of field indices. Changes in visual field indices (VFIs) and their slopes were assessed in each group and compared. RESULTS: Seventy-three persons were included in the study. Mean defect (MD) significantly improved (p = 0.001) from -9.52 ± 4.36 to -7.85 ± 4.36 dB during the study period in persons taking DHA + citicoline. Similarly, the mean VFI significantly improved (p = 0.001) in this group. The only treatment group showing a statistically significant improvement (p = 0.006) in the MD (from -0.1041 ± 0.2471 to 0.1383 ± 0.2544 dB/month) and VFI slope was the group treated with DHA+citicoline. CONCLUSIONS: The combination of oral treatment with DHA + citicoline significantly improved VF indices and their slopes in patients with glaucoma after 3 months of treatment.

Quantitative assessment of macular and circumpapillary retinal vessel density across all stages of Leber hereditary optic neuropathy using swept source optical coherence tomography angiography.

PURPOSE: To investigate the macular and circumpapillary retinal microvasculature across all stages of Leber hereditary optic neuropathy (LHON) using swept source optical coherence tomography angiography (OCTA). METHODS: This prospective, multicentre, cross-sectional, observational study analysed a total of 119 eyes of 60 patients with molecularly confirmed LHON across all stages and 120 eyes of 60 control subjects. Optical coherence tomography angiography maps centred on the fovea and optic disc were obtained to measure vessel densities (VDs) in the macular superficial (SCP) and deep (DCP) capillary plexuses, and the radial peripapillary capillary plexus (RPCP) respectively. RESULTS: In asymptomatic eyes, only the SCP showed significant changes on average (B coefficient = -0.72, 95% CI = -1.34 to -0.10, p = 0.022) or in sectors representing the papillomacular bundle (PMB) (B coefficient = -1.17, 95% CI = -2.23 to -0.11, p = 0.031). However, in chronic eyes, the greatest magnitude of change was found in the temporal sector of the RPCP (B coefficient = -12.36, 95% CI = -14.49 to -10.23, p < 0.001). The RPCP showed the strongest correlations with visual acuity (VA, logarithm of the minimum angle of resolution; R = -0.677, p < 0.001) and structural parameters (R = 0.747, p < 0.001). CONCLUSIONS: Retinal VD changes in the circumpapillary region of the PMB appear later than in the macula but end up being more profound and correlate better with VA and structural parameters. Further studies are needed to assess the clinical utility of retinal VDs as potential LHON biomarkers.

Interobserver and Intertest Agreement in Telemedicine Glaucoma Screening with Optic Disk Photos and Optical Coherence Tomography.

Purpose: To evaluate interobserver and intertest agreement between optical coherence tomography (OCT) and retinography in the detection of glaucoma through a telemedicine program. Methods: A stratified sample of 4113 individuals was randomly selected, and those who accepted underwent examination including visual acuity, intraocular pressure (IOP), non-mydriatic retinography, and imaging using a portable OCT device. Participants' data and images were uploaded and assessed by 16 ophthalmologists on a deferred basis. Two independent evaluations were performed for all participants. Agreement between methods was assessed using the kappa coefficient and the prevalence-adjusted bias-adjusted kappa (PABAK). We analyzed potential factors possibly influencing the level of agreement. Results: The final sample comprised 1006 participants. Of all suspected glaucoma cases (n = 201), 20.4% were identified in retinographs only, 11.9% in OCT images only, 46.3% in both, and 21.4% were diagnosed based on other data. Overall interobserver agreement outcomes were moderate to good with a kappa coefficient of 0.37 and a PABAK index of 0.58. Higher values were obtained by experienced evaluators (kappa = 0.61; PABAK = 0.82). Kappa and PABAK values between OCT and photographs were 0.52 and 0.82 for the first evaluation. Conclusion: In a telemedicine screening setting, interobserver agreement on diagnosis was moderate but improved with greater evaluator expertise.

Diagnostic Accuracy and Detection Rate of Glaucoma Screening with Optic Disk Photos, Optical Coherence Tomography Images, and Telemedicine.

PURPOSE: The aim of this study was to evaluate the diagnostic accuracy of optical coherence tomography (OCT) and retinography in the detection of glaucoma through a telemedicine program. METHODS: A population-based sample of 4113 persons was randomly selected. The screening examination included a fundus photograph and OCT images. Images were evaluated on a deferred basis. All participants were then invited to a complete glaucoma examination, including gonioscopy, visual field, and dilated fundus examination. The detection rate, sensitivity, specificity, and positive and negative predictive values were calculated. RESULTS: We screened 1006 persons. Of these, 201 (19.9%) were classified as glaucoma suspects; 20.4% were identified only by retinographs, 11.9% only by OCT images, and 46.3% by both. On ophthalmic examination at the hospital (n = 481), confirmed glaucoma was found in 58 (12.1%), probable glaucoma in 76 (15.8%), and ocular hypertension in 10 (2.1%), and no evidence of glaucoma was found in 337 (70.0%). The detection rate for confirmed or probable glaucoma was 9.2%. Sensitivity ranged from 69.4% to 86.2% and specificity from 82.1% to 97.4%, depending on the definition applied. CONCLUSIONS: The combination of OCT images and fundus photographs yielded a detection rate of 9.2% in a population-based screening program with moderate sensitivity, high specificity, and predictive values of 84-96%.

Evaluation of RETICs Glaucoma Diagnostic Calculators in Preperimetric Glaucoma.

PURPOSE: To evaluate two glaucoma diagnostic calculators (GDC) in a group of eyes with preperimetric glaucoma (PPG). METHODS: All eyes (n = 265) included in this study had ocular hypertension with normal visual fields (VFs) on repeated VF tests. PPG was defined as progression in the Guided Progression Analysis software from Cirrus-optical coherence tomography (GPA-OCT). Three PPG types were defined according to the GPA-OCT software as follows: (1) GPA-OCT with one or more red boxes in two or more columns; (2) GPA-OCT with two or more red boxes in two or more columns; and (3) GPA-OCT with two or more red boxes in two or more columns (definition 2), and in the last scan one or more red box in the RNFL average or quadrants. Nonparametric tests, areas under the receiver operating characteristic curve (AUC), and Bland-Altman tests were assessed. RESULTS: Definitions one, two, and three were met by 44 (16.6%), 29 (10.9%), and 11 (4.2%) eyes, respectively. The GDC indices (means ± standard deviations) were, respectively, 14.49 ± 21.55% and 26.06 ± 22.50% using the combined and quantitative GDC (P < 0.001) in all eyes. Both GDC showed higher glaucoma probability in the PPG group (P < 0.04; combined GDC AUCs, 0.720-0.833; quantitative GDC AUCs, 0.700-0.839). GDC values were higher (P < 0.01) with greater GPA progression. CONCLUSIONS: The values of both GDC were higher in the PPG group than the ocular hypertension group. The GDC were higher when more columns in the GPA software indicated progression. Both GDC showed a similar ability to detect PPG. TRANSLATIONAL RELEVANCE: These calculators facilitate diagnosis of PPG in ocular hypertensive eyes.

Cost and detection rate of glaucoma screening with imaging devices in a primary care center.

PURPOSE: To analyze the cost and detection rate of a screening program for detecting glaucoma with imaging devices. MATERIALS AND METHODS: In this cross-sectional study, a glaucoma screening program was applied in a population-based sample randomly selected from a population of 23,527. Screening targeted the population at risk of glaucoma. Examinations included optic disk tomography (Heidelberg retina tomograph [HRT]), nerve fiber analysis, and tonometry. Subjects who met at least 2 of 3 endpoints (HRT outside normal limits, nerve fiber index ≥30, or tonometry ≥21 mmHg) were referred for glaucoma consultation. The currently established ("conventional") detection method was evaluated by recording data from primary care and ophthalmic consultations in the same population. The direct costs of screening and conventional detection were calculated by adding the unit costs generated during the diagnostic process. The detection rate of new glaucoma cases was assessed. RESULTS: The screening program evaluated 414 subjects; 32 cases were referred for glaucoma consultation, 7 had glaucoma, and 10 had probable glaucoma. The current detection method assessed 677 glaucoma suspects in the population, of whom 29 were diagnosed with glaucoma or probable glaucoma. Glaucoma screening and the conventional detection method had detection rates of 4.1% and 3.1%, respectively, and the cost per case detected was 1,410 and 1,435€, respectively. The cost of screening 1 million inhabitants would be 5.1 million euros and would allow the detection of 4,715 new cases. CONCLUSION: The proposed screening method directed at population at risk allows a detection rate of 4.1% and a cost of 1,410 per case detected.

In vitro mitomycin C absorption and delivery with different sponge materials used in filtering surgery.

PURPOSE: The purpose of this study is to evaluate and compare mitomycin C (MMC) absorption and delivery in different materials used in filtering surgery. METHODS: This is an in vitro study comparing polyvinyl alcohol triangular sponges (TS6, TS8), polyvinyl alcohol fluid wicks (EFW), and absorbable gelatin sponges (AGS3, AGS5), from which five different types of transport units were obtained. Seven pieces of sponge of each transport unit type were obtained as follows: two transverse strips were obtained at 6 and 8 mm from the apex of TS and divided into three equal pieces; 4×4 mm pieces of EFW; 3×3 and 5×5 mm pieces of absorbable gelatin sponges were cut. Filter paper was placed on a precision scale (0.01 mg). The seven sponge pieces of each type were weighed three times consecutively in dry and wet states, the latter after immersion for 15 seconds in 0.2 mg/mL MMC. The difference between the weights of the dry and wet filter paper at the end of each measurement sequence was also calculated and considered as an estimate of the amount of mitomycin delivered. RESULTS: The amounts of MMC absorbed by each transport unit were as follows: (mean ± standard deviation) 27.43±5.13 for TS6, 31.91±6.63 for TS8, 15.96±2.23 for EFW, 17.96±2.05 for AGS3, and 33.81±2.05 for AGS5. The amounts of MMC delivered to the filter paper were as follows: 21.70±2.84 for TS6, 23.83±4.03 for TS8, 12.93±1.75 for EFW, 14.69±1.79 for AGS3, and 27.30±1.58 for AGS5. CONCLUSION: Percentage MMC delivered was similar for all materials, but there was a tendency for greater delivery using larger sponges and greater homogeneity in delivery with AGS5. No statistical differences were found in percentage delivered by the different transport materials.

Agreement among spectral-domain optical coherence tomography, standard automated perimetry, and stereophotography in the detection of glaucoma progression.

PURPOSE: The purpose of this study was to evaluate the agreement among spectral-domain optical coherence tomography, standard automated perimetry (SAP), and optic disc stereo photography in the detection of glaucomatous progression. METHODS: This was an observational cohort study enrolling 246 eyes (148 patients) followed for an average of 31.8 ± 9 months. Images were obtained every 6 to 12 months with optical coherence tomography (OCT), visual field test, and optic disc stereo photography. Progression was determined with OCT using guided progression analysis (GPA) software, in perimetry with Humphrey field analyzer GPA, and by masked assessment of stereo photograph series. Agreement among methods was reported using the κ coefficient, prevalence-adjusted bias-adjusted κ (PABAK), Gwet's first-order agreement coefficient (AC1), overall percentage agreement (OPA), percentage of positive agreement (Ppos), and percentage of negative agreement (Pneg). RESULTS: Progression by stereo photos, SAP, and OCT was found in 17 eyes (6.9%), 37 eyes (15%), and 63 eyes (25.6%), respectively. Most cases with detectable changes were only identified by one examination method, resulting in low Ppos (<33%). On the contrary, 147 eyes (59.7%) were identified as nonprogressing cases by all three methods, showing high OPA (72.8-89.8) and high Pneg (83.8-94.5). PABAK and AC1 between methods reached 0.67 to 0.88. Measurements of agreement showed a trend toward better agreement between photos and visual field (VF) than between photos and OCT. Spectral-domain OCT parameters reflected a tendency toward better agreement with stereo photos than with VF. CONCLUSIONS: Methods obtained acceptable agreement outcomes in terms of PABAK, AC1, and OPA. However, most cases with detectable changes were identified only by one examination method, resulting in low Ppos.

Multichannel functional testing in normal subjects, glaucoma suspects, and glaucoma patients.

PURPOSE: To evaluate visual function with a novel multichannel functional test named the ATD Multichannel Functional Test. METHODS: This multicenter study had a prospective and cross-sectional design. A total of 186 eyes were included: 42 with glaucoma, 14 glaucoma suspects due to optic nerve characteristics, 25 ocular hypertensives, and 105 normal eyes. All patients performed standard visual fields (Humphrey 24-2) and ATD with eight stimuli configurations: four achromatic (A), two red-green (T), and two blue-yellow (D). To derive main outcome measures, mean sensitivity, mean defect (MD), and pattern standard deviation (PSD) were calculated and compared among groups and types of stimuli with the Kruskal-Wallis test. The percentage of cases outside normal limits (ONL) was calculated. RESULTS: MD and PSD were significantly different in glaucoma eyes than in normal subjects for all types of stimuli except D-0.5 cycles per degree (cpd)/12Hz. PSD was also lower for normals than for all pathologic groups with A-4cpd/2Hz, A-4cpd/12Hz, D-0.5cpd/2Hz, and T-0.5cpd/2Hz. The highest percentage of ONL cases was obtained with the two low-spatial-frequency chromatic stimuli, with D-0.5cpd/2Hz and T-0.5cpd/2Hz using PSD, which classified as ONL 81.6% and 86.7% of glaucoma eyes, 51.8% and 44.5% of hypertensives, and 72.2% and 41.2% of optic disc suspects, respectively. CONCLUSIONS: ATD assessed different aspects of visual function, and the most sensitive tests to detect glaucomatous damage were the low-temporal-frequency chromatic tests.

Exposure to a controlled adverse environment impairs the ocular surface of subjects with minimally symptomatic dry eye.

PURPOSE: Adverse environmental conditions elicit dry eye (DE)-related signs and symptoms. The purpose of this work is to determine whether these conditions can alter a normal-to-borderline ocular surface in subjects with DE symptoms. METHODS: Ten minimally symptomatic contact lens (CL)-wearing subjects were exposed, without (WO-) and with (W-)CLs, to a controlled adverse environment (CAE) of 22.0 +/- 2.0 degrees C and 19.0% +/- 4.0% relative humidity (RH) for 2 hours in an environmental chamber (EC). One month later, the same subjects were placed in an indoor normal environment (INE) of 24.2 +/- 1.3 degrees C and 34.8% +/- 2.9% RH for 2 hours. DE-related signs and symptoms were evaluated before and after each exposure. The reversibility of changes provoked by CAE or INE was also evaluated. RESULTS: Without CL wear, significant changes were found in DE signs (noninvasive tear break-up time [NIBUT], conjunctival hyperemia and phenol red thread test) after CAE exposure, but not found after INE exposure. However with CL wear, the same tests were altered after both CAE and INE exposure. Most of these changes returned to normal values within 1 month after environmental exposure. CONCLUSIONS: Significant changes in comfort and the ocular surface tests were found after 2 hours of exposure to CAE. These results show the negative impact that an adverse environment, especially low RH, can have on the ocular surface. These alterations were fully reversible. This indicates that the CAE is a safe and functional condition in which to standardize DE diagnostic tests and evaluate therapeutics.

Efficacy of five human melanocytic cell lines in experimental rabbit choroidal melanoma.

This study was undertaken to compare the ability of five uveal melanocytic cell lines to produce primary and metastatic uveal melanomas in immunosuppressed rabbits and to determine whether animal survival was improved by antibiotic administration. One hundred albino rabbit eyes, five groups of 20, were implanted in the suprachoroidal space with four melanoma cell lines (MKT-BR, OCM-1, 92-1 and SP 6.5) and one melanocytic line (UW-1). Rabbits were immunosuppressed with cyclosporin A (CsA) at a dosage of 15 mg/kg/day, decreased to 10 mg/kg/day after the fourth week. Prophylactic penicillin G, 10 to 2 x 10 IU, was administered intramuscularly at 5-day intervals. Animals were followed for 12 weeks and the ophthalmoscopic findings, weight and general well-being were recorded weekly. Autopsies were performed to study the eyes, liver and lungs under light microscopy. The mean global survival time in the groups was 43+/-4 days. Ophthalmoscopic intraocular tumours developed in 37% of the MKT-BR group, 50% of the OCM-1 group, 100% of the 92-1 group, 23% of the UW-1 group and 75% of the SP 6.5 group; histologically, tumours appeared in 36.8%, 45%, 100%, 58.8% and 100%, respectively. The 92-1 and SP 6.5 cell lines were associated with the most aggressive local behaviour. Lung metastases developed in the OCM-1 group (5%), 92-1 group (61.1%), UW-1 group (7.1%) and SP 6.5 group (42.1%), but were not present in the MKT-BR group. The 92-1 and SP 6.5 cell lines were the most efficient in local and metastatic tumour production. Prophylactic antibiotic administration did not improve animal survival.

Animal models in uveal melanoma: establishment and research.

Experimental models may help elucidate aspects of uveal melanoma, such as the histogenesis, etiology and natural history, that are not yet fully understood. Moreover, the development of experimental models allows testing of new diagnostic methods and treatments to improve the life expectancy and quality of life of affected patients. The author reviews the development of animal models of uveal melanoma and research with animal models examining primary and metastatic uveal melanoma as well as treatments for these tumours and ways to prevent metastasis.