Saverio Luccarelli

The dynamic healing process of idiopathic macular holes after surgical repair: a spectral-domain optical coherence tomography study.

PURPOSE To analyze progressive changes of the outer retina after vitrectomy for macular hole (MH) repair. METHODS Nineteen consecutive patients underwent vitrectomy for idiopathic MH. Spectral domain optical coherence tomography (SD-OCT) examinations were performed pre- and postoperatively during follow-up visits at 1, 3, 6, 9, and 12 months. Active eye-tracking technology ensured that the same scanning location was identified each time. RESULTS Ten eyes showed a normal external limiting membrane (ELM) at 1 month after surgery and 15 eyes at 3 months. The ELM was already continuous in 79% of the eyes with persistent outer foveal defects during follow-up. No eyes revealed a continuous inner segment/outer segment (IS/OS) line at 1 month, only one eye at 3 months, and 10 eyes at 12 months. No eyes had a disrupted ELM with an intact IS/OS line. Foveal cysts were visible in three eyes at 1 month and in eight eyes during follow-up. The cystic space gradually filled, resulting in a continuous IS/OS line in five of these eyes. Recovery of ELM, IS/OS, and outer nuclear layer (ONL) determined most of visual acuity improvement. The ONL appeared normal in the 10 eyes with an intact IS/OS line at last follow-up. By contrast, it was disrupted in 7 of 9 eyes with a final persistent outer foveal defect. CONCLUSIONS The ELM is the first structure to recover after MH closure. Foveal cysts may develop during follow-up, and in the presence of an intact ONL, they may gradually fill with complete recovery of the IS/OS junction.

Artifacts in automatic retinal segmentation using different optical coherence tomography instruments.

Purpose: The purpose of this study was to compare and evaluate artifact errors in automatic inner and outer retinal boundary detection produced by different time-domain and spectral-domain optical coherence tomography (OCT) instruments. Methods: Normal and pathologic eyes were imaged by six different OCT devices. For each instrument, standard analysis protocols were used for macular thickness evaluation. Error frequencies, defined as the percentage of examinations affected by at least one error in retinal segmentation (EF-exam) and the percentage of total errors per total B-scans, were assessed for each instrument. In addition, inner versus outer retinal boundary delimitation and central (1,000 &mgr;m) versus noncentral location of errors were studied. Results: The study population of the EF-exam for all instruments was 25.8%. The EF-exam of normal eyes was 6.9%, whereas in all pathologic eyes, it was 32.7% (P < 0.0001). The EF-exam was highest in eyes with macular holes, 83.3%, followed by epiretinal membrane with cystoid macular edema, 66.6%, and neovascular age-related macular degeneration, 50.3%. The different OCT instruments produced different EF-exam values (P < 0.0001). The Zeiss Stratus produced the highest percentage of total errors per total B-scans compared with the other OCT systems, and this was statistically significant for all devices (P ≤ 0.005) except the Optovue RTvue-100 (P = 0.165). Conclusion: Spectral-domain OCT instruments reduce, but do not eliminate, errors in retinal segmentation. Moreover, accurate segmentation is lower in pathologic eyes compared with normal eyes for all instruments. The important differences in EF among the instruments studied are probably attributable to analysis algorithms used to set retinal inner and outer boundaries. Manual adjustments of retinal segmentations could reduce errors, but it will be important to evaluate interoperator variability.

Automated Software Analysis of Corneal Micrographs for Peripheral Neuropathy

PURPOSE A relationship has been reported between the presence of peripheral neuropathy and the density and shape of corneal nerve fibers. Peripheral neuropathy is a debilitating condition that arises from many common health problems, and its presence is often confirmed with an invasive clinical test called intramuscular electromyography (EMG). In this study, the possibility of developing an alternative or adjunct test to EMG based on the appearance of nerve fibers in corneal micrographs was explored. Since corneal imaging is virtually noninvasive compared with EMG, such a test may be administered more liberally and frequently, before neuropathy symptoms occur. METHODS A software program that automatically traces nerve fibers in corneal micrographs and generates measures based on these traces was implemented. This software was applied to a database of images collected by confocal laser scanning corneal microscopy from diabetic subjects whose levels of neuropathy were measured with EMG and from healthy subjects. RESULTS Trends in the nerve fiber density and various measures of shape were calculated and observed, to explore the possibility of using these measures as a clinical tool for corroborating symptoms, confirming an evaluation, or evaluating risk factors for developing neuropathy. CONCLUSIONS Preliminary statistical trends show a potential for measuring and observing neuropathy severity or for providing an objective risk measure for a patients ensuing condition. More work is needed in the development of the measures and in their testing to prove that the measures can be made repeatable in a clinical environment.

Evaluation of prostaglandin analogue effects on corneal keratocyte density using scanning laser confocal microscopy.

PurposeTo determine if treatment with prostaglandin (PG) analogues affects keratocyte density as an indirect measure of extracellular matrix in the corneal stroma. Patients and MethodsIn this case control study, 129 eyes from 68 patients were examined: 52 eyes had only PG analogue therapy for at least 3 years, 37 eyes had only &bgr;-adrenergic blocker therapy for at least 3 years, and 40 control eyes were without therapy. Scanning laser confocal microscopy was carried out, and each corneal stroma was subdivided into the anterior, midstroma, and posterior stroma. Keratocyte density was determined from the images by manual counting. ResultsKeratocyte densities in the entire stroma and in 2 stromal layers were significantly higher in patients with PG analogue therapy compared with control patients (entire stroma, P<0.001; anterior stroma, P=0.001; posterior stroma, P=0.016). Keratocyte density in the PG analogue therapy patients was also greater compared with the &bgr;-adrenergic blocker patients (entire stroma, P<0.001; anterior stroma, P<0.001; mid-stroma P=0.023, posterior stroma P=0.007). There were no significant differences between the control and &bgr;-adrenergic blocker groups. Overall, the density increase for the PG analogue group was greatest in the anterior stroma. ConclusionsPG analogue therapy increased the keratocyte density in each layer of corneal stroma, but more significantly in the anterior stroma than in the midstroma or the posterior stroma. The increased keratocyte density might be the result of diminished extracellular matrix, possibly owing to the known activation of matrix metalloproteinases and inhibition of tissue inhibitors of the metalloproteinases.

Dry Eye in Vernal Keratoconjunctivitis: A Cross-Sectional Comparative Study.

Abstract The purpose of this comparative cross-sectional study was to investigate the use of standardized clinical tests for dry eye in pediatric patients with active and quiet vernal keratoconjunctivitis (VKC) and to compare them with healthy children. We recruited 35 active VKC, 35 inactive VKC, and 70 age-matched control healthy subjects. Each child underwent a complete eye examination, including visual analog scale symptoms assessment, biomicroscopy, fluorescein break-up time (BUT), corneal fluorescein and conjunctival lissamine green staining, corneal esthesiometry, Schirmer test with anesthetic, and meibomian glands inspection and expression. Active VKC patients showed significantly increased symptoms and signs of ocular surface disease, compared with the other 2 groups. Inactive VKC patients, compared with control subjects, showed increased photophobia (P < 0.05; Mann-Whitney U test), conjunctival lissamine green staining and Schirmer test values, and reduced BUT and corneal sensitivity [P < 0.05 by analysis of variance (ANOVA) least significant difference posthoc test for BUT and Schirmer; P < 0.001 by Mann-Whitney U test for lissamine green staining and corneal sensitivity]. Our results confirm the association between VKC and short-BUT dry eye. This syndrome seems to affect the ocular surface in quiescent phases too, determining abnormalities in tear film stability, epithelial cells integrity, and corneal nerves function. The very long-term consequences of this perennial mechanism of ocular surface damage have not been fully understood yet.

Image analysis software for following progression of peripheral neuropathy

A relationship has been reported by several research groups [1 - 4] between the density and shapes of nerve fibers in the cornea and the existence and severity of peripheral neuropathy. Peripheral neuropathy is a complication of several prevalent diseases or conditions, which include diabetes, HIV, prolonged alcohol overconsumption and aging. A common clinical technique for confirming the condition is intramuscular electromyography (EMG), which is invasive, so a noninvasive technique like the one proposed here carries important potential advantages for the physician and patient. A software program that automatically detects the nerve fibers, counts them and measures their shapes is being developed and tested. Tests were carried out with a database of subjects with levels of severity of diabetic neuropathy as determined by EMG testing. Results from this testing, that include a linear regression analysis are shown.