CHANGES IN TOTAL AND INNER RETINAL THICKNESSES IN TYPE 1 DIABETES WITH NO RETINOPATHY AFTER 8 YEARS OF FOLLOW-UP.

PURPOSE: To evaluate changes in retinal layer thickness in patients with Type 1 diabetes with no diabetic retinopathy after 8 years of follow-up. METHODS: Ninety Type 1 diabetes and 60 control eyes were studied. Changes in the retinal nerve fiber layer, ganglion cell layer, and inner nuclear layer thicknesses in all Early Treatment Diabetic Retinopathy Study areas were evaluated. RESULTS: The mean ages were 42.93 ± 13.62 and 41.52 ± 13.05 years in the diabetic and control group, respectively. In 2009, total retinal thickness was higher in diabetic patients; differences were statistically significant in all except the nasal areas. In both groups, the mean foveal thickness remained the same during the 8 years. Among diabetic patients, there was a significant reduction in total retinal thickness in all areas excluding the outer temporal one; controls only in the inferior areas. The thickness loss was due to the thinning of the inner retinal layers (inner nuclear layer, ganglion cell layer, and retinal nerve fiber layer). The controls showed a significant diminution in the retinal nerve fiber layer and in the ganglion cell layer areas. The inner nuclear layer showed a diminution in the diabetes mellitus group. CONCLUSION: Before the onset of diabetic retinopathy, Type 1 diabetes patients experience a diminution of their inner retinal layer thicknesses over time, supporting the hypothesis of retinal neurodegeneration.

Interocular Symmetry of Choroidal Thickness and Volume in Healthy Eyes on Optical Coherence Tomography.

BACKGROUND: We aimed to determine the physiological symmetry, with spectral-domain optical coherence tomography, of choroidal measurements in a healthy population in all the areas defined in the Early Treatment Diabetic Retinopathy Study (ETDRS). METHODS: One hundred and fifty-four eyes of 77 healthy young adults between the ages of 19 and 32 years were enrolled. Differences in choroidal thickness (CT) and volume (CV) between the left and right eyes were calculated. Normal ranges of absolute interocular differences were established as the 95th percentile. RESULTS: The mean ± SD subfoveal CT (SFCT) and total CV values in the right and left eyes were 342.03 ± 77.38 versus 361.64 ± 76.45 µm (correlation coefficient ρ = 0.820; p < 0.001) and 0.27 ± 0.06 versus 0.28 ± 0.06 mm3 (ρ = 0.830; p < 0.001), respectively. Differences in 5 of the 9 areas of the ETDRS map were statistically significant (p < 0.05), but with a strong interocular correlation (ρ > 0.8; p < 0.001). The 95th percentile of interocular tolerance limits for CT in the 1-, 3-, and 6-mm areas were 97, 70, and 57 µm, respectively; the 95th percentile for the volume values were 0.06, 0.51, and 1.73 mm3. CONCLUSIONS: CT and CV are highly correlated between eyes, statistically significant differences between them can be found, and absolute interocular differences may reach 97 µm in SFCT, and 1.73 mm3 in total CV.

BLINDNESS RELATED TO PRESUMED RETINAL TOXICITY AFTER USING PERFLUOROCARBON LIQUID DURING VITREORETINAL SURGERY.

PURPOSE: To describe the presumed retinal toxicity after using specific batches of perfluorocarbon liquid ALA OCTA (Alamedics, Dornstadt, Germany) in pars plana vitrectomy. METHODS: This is an observational retrospective consecutive case series analyses of patients operated on pars plana vitrectomy for retinal detachment or intraocular lens subluxation, using the 150141 or 200114 batches of perfluorocarbon liquid ALA OCTA as assistance during the surgery in a single center. Patients were included in this report if they manifested retinal toxicity signs throughout the follow-up, such as retinal and retinal pigment epithelium atrophy, disk paleness, and intensive macular fibrosis. Spectral domain optical coherence tomography (Spectralis; Heidelberg Engineering, Heidelberg, Germany) and Ultra-Wide Field 200° retinal camera (Optos P200Tx; Optos, Scotland, United Kingdom) images, electrophysiological tests, and visual fields were performed to analyze the retinal structure and functionality. RESULTS: Seven of 80 patients showed all the described signs of toxicity, after a mean follow-up of 34.29 days (range: 10-87) since surgery. Four patients needed a second pars plana vitrectomy because of tractional retinal detachment and proliferative vitreoretinopathy, and two of them underwent a third surgery because of redetachment. All patients experienced amaurosis or central scotoma, with a final best-corrected visual acuity ranging from 20/200 to light perception. CONCLUSION: Presumed toxic batches of perfluorocarbon liquid may cause massive retinal toxicity. A rapid suspicion, a correct traceability of surgical products, and informing health authorities are fundamental to prevent further cases of toxicity.

ACUTE RETINAL DAMAGE AFTER USING A TOXIC PERFLUORO-OCTANE FOR VITREO-RETINAL SURGERY.

PURPOSE: To describe a series of retinal acute toxicity cases with severe visual loss after intraocular use of a toxic perfluoro-octane (PFO). The clinical presentation is described, and the likely causes are analyzed. New biological methods for testing safety of intraocular medical devices are proposed. METHODS: Information regarding a series of eyes suffering acute severe events after intraocular use of a toxic PFO was analyzed. Four types of spectroscopy, nuclear magnetic resonance, and chromatography were used to identify the potential PFO contaminants. Cultures of human retinal pigment epithelial cells (ARPE-19) and porcine neuroretina were used to quantify the toxicity of the suspect PFO lots. RESULTS: Of 117 cases of intraocular toxicity, 96 were considered clearly related to the use of PFO. Fifty-three cases had no light perception, and 97 had no measurable visual acuity. Retinal necrosis (n = 38) and vascular occlusion (n = 33) were the most characteristic findings. Two hydroxyl compounds, perfluorooctanoic acid and dodecafluoro-1-heptanol, and benzene derivatives were identified as the suspected toxic agents. While existing toxicity testing failed, we proposed new tests that demonstrated clear toxicity. CONCLUSION: Protocols to determine cytotoxicity of intraocular medical devices should be revised to assure safety. Acute toxic events should be reported to health authorities and scientific media.

Prevalence of Vitreoretinal Interface Abnormalities on Spectral-Domain OCT in Healthy Participants over 45 Years of Age.

PURPOSE: To assess the prevalence of vitreoretinal interface abnormalities in a general population of healthy adults ≥45 years of age. DESIGN: Cross-sectional study carried out at 17 ophthalmology services throughout Spain. PARTICIPANTS: Between September 2015 and March 2016, all consecutive healthy persons aged ≥45 years who were accompanying patients to ophthalmology services were invited to take part in the study. Exclusion criteria were known retinal disease, uveitis, history of ocular trauma or previous intraocular surgery (including cataract surgery and intravitreal injections), severe myopia (>-6 dioptres), and poor ocular media transparency. METHODS: Spectral-domain OCT or swept-source OCT was performed on all participants. Diseases of the vitreomacular interface were classified according to the OCT-based anatomic classification system of the International Vitreomacular Traction Study Group. All pathologic and borderline images as well as doubtful cases were evaluated blindly in a central reading center. MAIN OUTCOME MEASURES: Prevalence of vitreomacular interface abnormalities (vitreomacular traction epiretinal membrane, lamellar hole). RESULTS: The study included 2257 participants with a mean age of 59.5 years (range 45-90), and a total of 4490 eyes (right eyes 2242, left eyes 2248). Vitreoretinal interface abnormalities were detected in 70 eyes, with a prevalence of 1.6%. Vitreomacular adhesion was observed in 1317 eyes (29.3%). Results of spectral-domain OCT or swept-source OCT examination were unrevealing in 3103 eyes. Vitreoretinal interface abnormalities were found in 61 participants, with a prevalence in the study population of 2.7%. Vitreomacular traction was observed in 14 participants (0.6%), epiretinal membrane in 44 (1.9%), and lamellar macular hole in 3 (0.1%). The prevalence of both vitreomacular traction and epiretinal membrane increased significantly with age. The presence of vitreoretinal interface abnormalities was unrelated to concomitant diabetes mellitus or hypertension. CONCLUSIONS: An important percentage of healthy participants from the general population ≥45 years of age showed vitreoretinal interface abnormalities. Screening with OCT is advisable at any first routine consultation or preoperative assessment, particularly in older participants.

Choroidal thickness and volume in healthy young white adults and the relationships between them and axial length, ammetropy and sex.

PURPOSE: To evaluate choroidal thickness in young adults using enhanced-depth imaging spectral-domain optical coherence tomography and to describe volume differences in all the areas defined in the Early Treatment Diabetic Retinopathy Study. DESIGN: Prospective clinical study. METHODS: In 95 healthy young (23.8 ± 3.2 years) adult volunteers, 95 eyes were prospectively enrolled. Manual choroidal segmentation on a 25-raster horizontal scan protocol was performed. The measurements of the 9 subfields defined by the Early Treatment Diabetic Retinopathy Study were evaluated. RESULTS: Mean subfoveal choroidal thickness was 345.67 ± 81.80 µm and mean total choroidal volume was 8.99 ± 1.88 mm(3). Choroidal thickness and volume were higher in the superior and temporal areas than in the inferior and nasal sectors of the same diameter, respectively. Strong correlations between subfoveal choroidal thickness and axial length and myopic refractive error were obtained (r = -0.649, P < 0.001, and r = 0.473, P < 0.001, respectively). Emmetropic eyes tended to have thicker subfoveal choroidal thickness (381.94 ± 79.88 µm vs 307.04 ± 64.91 µm) and higher total choroidal volume than myopic eyes (9.80 ± 1.87 mm(3) vs 8.14 ± 1.48 mm(3)). The estimation of the variation in the subfoveal choroidal thickness in relationship to the axial length was -43.84 µm/mm. In the myopic group, the variation in the subfoveal choroidal thickness with the myopic refractive error was -10.45 µm per diopter. CONCLUSIONS: This study establishes for the first time a normal database for choroidal thickness and volume in young adults. Axial length, and myopic ammetropy are highly associated with choroidal parameters in healthy subjects. Enhanced-depth imaging spectral-domain optical coherence tomography exhibited a high degree of intraobserver and interobserver repeatability.

Changes in frequency-doubling perimetry in patients with type I diabetes prior to retinopathy.

PURPOSE: To evaluate the ability of frequency-doubling technology (FDT) perimetry in detecting visual field defects in young adults with type I diabetes prior to retinopathy or with minor retinovascular changes. METHODS: This comparative cross-sectional study included 30 healthy subjects and 73 age-matched patients with type I diabetes mellitus. All subjects underwent a full ocular examination including an FDT with the threshold C-20-5 strategy. Only one eye per subject was randomly included in the statistical analysis. FDT results and time to perform the test were compared between the groups. RESULTS: The mean age was 27.1 years in the control group and 26.6 years in the diabetic group (P = 0.875). The mean period from the onset of diabetes was 12.6 ± 6.7 years, while minimal retinovascular changes were observed in 18 eyes. Mean deviation of FDT did not differ between the groups. Although global indices of FDT were within normal limits, pattern standard deviation of FDT was higher in the diabetic group (P = 0.035). The area under the receiver operating characteristic curve was 0.647 for pattern standard deviation of FDT (standard error = 0.052; P = 0.017). CONCLUSION: FDT can detect retinal dysfunctions in diabetic patients prior to the onset of significant vascular complications.

Reproducibility and repeatability of Cirrus and Spectralis Fourier-domain optical coherence tomography of healthy and epiretinal membrane eyes.

PURPOSE: To evaluate the accuracy and reproducibility of retinal thickness measurements in healthy and epiretinal membranes (ERM) eyes by Cirrus and Spectralis Fourier-domain optical coherence tomography devices. METHODS: Eighty-seven ERM and 122 healthy subjects underwent 3 macular scans using both optical coherence tomography instruments. Mean thickness measurements in the nine Early Treatment Diabetic Retinopathy Study areas were compared, evaluating the repeatability and the relationship between devices. RESULTS: Macular thickness increase was detected in ERM eyes for all optical coherence tomography parameters (P < 0.001). Mean foveal thickness was 423.5 ± 81.4 and 438.0 ± 54.2 µm for ERM eyes and 267.1 ± 20.2 and 277.5 ± 18.9 µm for healthy eyes using Cirrus and Spectralis, respectively. Macular average thickness in ERM eyes as determined by both optical coherence tomography was correlated (r = 0.812; P < 0.001) but significantly different (P = 0.044). In ERM eyes, measurements showed a mean of the coefficients of variation of 2.95%, 2.2%, and 1.01% using Cirrus, Spectralis, and Spectralis progression feature, respectively. Intraclass correlation coefficients were higher than 0.919 in all cases. CONCLUSION: Reproducibility of both Cirrus and Spectralis optical coherence tomography was high in healthy and ERM eyes. However, considerable differences were found between macular thickness measurements obtained by both devices despite the high correlation between them.