Pietro Emanuele Napoli

Qualitative and quantitative analysis of filtering blebs with optical coherence tomography

OBJECTIVE To provide a qualitative and quantitative analysis of filtering blebs with optical coherence tomography (OCT) in patients after primary trabeculectomy. DESIGN Evaluation of diagnostic technology. PARTICIPANTS We retrospectively studied 20 eyes of 20 patients who had a fornix-based flap in primary trabeculectomy: 14 with mitomycin C (MMC) and 6 without MMC. METHODS Filtering blebs were examined using 2 types of OCTs working at a wavelength of 840 and 1310 nm. In this study, we analyzed both the OCT morphologic pattern and the internal structures of blebs, including bleb wall thickness, scleral flap thickness, and the route under the scleral flap, and quantified the reflectivity of the intrableb area. RESULTS Blebs were classified according to the Hirooka scheme in 3 OCT morphologic patterns: cystoid, diffuse, and layer type. The MMC was associated with the surgical success (100%). A significant association was found between good functionality and cystoid type with both devices: 840-nm OCT (p = 0.02) and 1310-nm OCT (p = 0.04). A significant difference in morphologic patterns was found using the 2 OCTs. There were no significant differences between successful and unsuccessful filtering surgery for intrableb structures. The reflectivity of filtering blebs correlated very well to the postoperative intraocular pressure (IOP; R(2) = 0.90; p < 0.001) and to the reduction of IOP (R(2) = 0.58; p = 0.001). Our method to quantify the reflectivity showed a significant degree of intergrader consensus (intraclass correlation coefficient = 0.99; p < 0.001). CONCLUSIONS Although 840-nm OCT was not developed to assess the anterior segment, it may be considered a useful tool to evaluate the functionality of blebs in the postoperative period.

A novel technique of contrast-enhanced optical coherence tomography imaging in evaluation of clearance of lipids in human tears.

Purpose The aim of this work was to gather preliminary data in different conditions of healthy eyes, aqueous tear deficient dry eyes, obstructive meibomian gland disease (MGD) and non-obvious obstructive MGD (NOMGD) individuals, using a new, contrast-enhanced optical coherence tomography (OCT) imaging method to evaluate the clearance of lipids in human tears. Methods Eighty-two adult patients presenting with complaints of ocular irritation were studied for abnormalities of the ocular surface and classified as healthy (n = 21), aqueous tear deficient dry eyes (n = 20), obstructive MGD (n = 15) and NOMGD (n = 26) individuals. A lipid-based tracer, containing an oil-in-water emulsion, was used to obtain an enhanced OCT imaging of the lower tear meniscus. After instillation, a dramatic initial increase of reflectivity of the lower tear meniscus was detected by OCT, followed by a decay back to baseline values over time. Based on this finding, the clearance of lipids was measured in real-time by Fourier-domain anterior segment OCT. Results The differences in the clearance of lipids among the four groups as well as the correlations between symptom questionnaire score, standardized visual scale test, fluorescein break-up time, ocular surface fluorescein staining score, Schirmer I test scores were found to be statistically significant. The individual areas under the curve of the clearance of lipids calculated by the receiver operating characteristic curve technique ranged from 0.66 to 0.98, suggesting reliable sensitivity and specificity of lipid-enhanced OCT imaging. Conclusions This new technique of contrast-enhanced OCT imaging of the tear film following lipid-based tracer instillation provides a measure of the clearance of lipids. The quantitative values found are in agreement with other methods of evaluation of the lacrimal system. An improvement of the clinicians ability in the diagnosis and understanding of abnormalities of the ocular surface may be achieved by this simple approach.

Evaluation of the Adhesive Properties of the Cornea by Means of Optical Coherence Tomography in Patients with Meibomian Gland Dysfunction and Lacrimal Tear Deficiency

Objective The aim was to determine the influence of meibomian gland dysfunction (MGD) and aqueous tear deficiency dry eye (ADDE) on the adhesive properties of the central cornea by means of optical coherence tomography (OCT), and to investigate the relationship between corneal adhesiveness and classical tear tests, as well as the reliability of results, in these lacrimal functional unit disorders. Design Prospective, case-control study. Methods Twenty-eight patients with MGD and 27 patients with ADDE were studied. A group of 32 healthy subjects of similar age and gender distribution served as a control group. The adhesive properties of the anterior corneal surface were measured by OCT, based on the retention time of adhesion marker above it, in all participants. Results An excellent (≥5 minutes), borderline (within 3–5 minutes), fair (within 1–3 minutes) and poor (<1 minute) values of corneal adhesiveness were found, respectively, in 0%, 7.1%, 64.3% and 28.6% of MGD, in 0%, 7.4%, 63% and 29.6% of ADDE, and in 31.3%, 65.6%, 3.1% and 0% of healthy patients. The differences in time of corneal adhesiveness between MGD and healthy patients, as well as between ADDE and healthy patients, were found to be statistically significant (p<0.001; p<0.001; respectively). Conversely, no statistical significant differences between MGD and ADDE were found (p = 0.952). Data analysis revealed a statistically significant correlation between corneal adhesiveness and clinical tests of dry eye, as well as an excellent degree of inter-rater reliability and reproducibility for OCT measurements (p<0.001). Conclusion ADDE and MGD share similar abnormalities on OCT imaging. Decreased adhesive properties of the anterior cornea were identified as a common feature of MGD and ADDE. This simple OCT approach may provide new clues into the mechanism and evaluation of dry eye syndrome.

Post-Mortem Corneal Thickness Measurements with a Portable Optical Coherence Tomography System: a Reliability Study.

The purpose of this study was to determine the repeatability and reproducibility of post-mortem central corneal thickness (CCT) measurements by using a real-time, portable optical coherence tomography (OCT) system on an animal model, and to prospectively evaluate the time-course of post-mortem changes in CCT. Forty-six ocular globes of sheep (Ovis aries) were analyzed with a portable spectral-domain OCT device by two operators at different postmortem intervals (PMIs) as follows: immediately (i.e. within 10 minutes), at the 30th minute, at the 1st, 6th, 12th, 24th and 48th hour, and later (up to the 96th hour). The coefficient of repeatability ranged from 0.3% to 3.5%, and coefficients of reproducibility ranged from 0.2% to 3.7% in the central region of the cornea. The intraclass correlation coefficients were particularly high at different PMIs, thus confirming good measurement reliability with the portable OCT. The average CCT decreased immediately and then increased thereafter, with two peaks at 6 and 24 hours after death. Our results suggest that portable OCT is a reliable tool for monitoring CCT variations after death and may be useful in characterizing corneas before explantation, detecting quantitative variations during post-mortem corneal degeneration or assessing changes in CCT for forensic implications.

A Simple Novel Technique of Infrared Meibography by Means of Spectral-Domain Optical Coherence Tomography: A Cross-Sectional Clinical Study

Purpose To compare a novel spectral-domain optical coherence tomography (SD-OCT) technique with traditional lid transillumination for evaluation of meibomian glands (MGs) and to assess the relation of MG morphologic changes to the glandular atrophy. Design Evaluation of diagnostic technology. Participants Sixty-one patients with obstructive MGD (30 men, 31 women; age [mean ± standard deviation] 45.1 ± 12.1 years), and 75 control subjects (32 men, 43 women; 44.1 ± 12.5 years) were recruited in order to have a balanced distribution of glandular features. Methods Agreement between SD-OCT and lid transillumination examination for the detection of drop-out (partial or complete loss of MGs) and microscopic changes (i.e. shortening, distortion, segmentation and entanglement), as well as the relationship between morphological features and MG atrophy were evaluated. Main Outcome Measures Agreement between the two meibographic techniques, bias in symmetry of classification, and association analysis between microscopic changes and MG dropout. Results Overall agreement for all morphological features was substantial (Cohen kappa coefficient = 0.77; p<0.001), even if, the majority of disagreement occurred for cases with segmentation, where agreement was present in only 108 (81.82%) of 132 eyes with adequate images for interpretation, and where SD-OCT tended to diagnose more cases not detected by traditional lid transillumination (McNemar test, p<0.001). Moreover, segmentation and distortion pattern negatively correlated with the degree of drop-out, whereas shortening and entanglement pattern demonstrated only a weak correlation (Spearman’s ρ was -0.691, -0.491, -0.359, -0.385, respectively). Conclusions Each method has its advantages but in general there was close agreement between these meibographic techniques, particularly for MG dropout, which supports the reliability of our novel, simple and patient-friendly SD-OCT approach.

Morphological analysis of corneal findings modifications after death: A preliminary OCT study on an animal model

&NA; The aim of this work was to describe, for the first time, the morphological modifications, in a three‐dimensional mode, of the central cornea at different intervals since death. The study design involved the analysis of 30 eyes (15 heads) of female, adult sheep (>2 years) sacrificed at a local slaughterhouse. The eyes, after animal decapitation, were examined in situ, without enucleation. Ocular globes were stored at well‐known temperature (within a range of 12–22 °C) and humidity (within a range of 50–60%). The instrumental analysis was executed using a portable spectral‐domain OCT (SD‐OCT) system (iVue SD‐OCT, Optovue Inc, Fremont, CA) calibrated to the corneal mode. OCT imaging was performed at different time‐points since death. Pachymetric map, morphological and ultrastructural analysis (epithelium, stroma, and endothelium), were performed for each time‐point. After an initial thinning of tissues and an enhancement of epithelial reflectivity, stromal thickness increased from the 2nd up to the 6th hour. Subsequently, a new trend incorneal thinning was observed in association with the appearance ofone or more demarcation lines between the anterior andposterior stroma. After the 12th hour, a recurrence of corneal swelling was detected in association with thedelamination of stromal tissue. Since the 24th hour, the epithelium disappeared in 50% of cases and the anterior chamberdepth progressively decreased. At the 48th hour, various ocular structures showed the onset of putrefaction processes, such as theappearance of hyper‐reflective dots in anterior chamber, iridocorneal contact, and the massive vacuolization of theposterior stroma until the total delamination. The portable OCT system is a useful approach for in situ postmortem corneal examination, and it may be potentially applied for the selection of donor cornea in transplantology and for the determination of post‐mortem intervals in forensic medicine.

Resolution of pinguecula-related dry eye disease after argon laser photocoagulation

Purpose To describe an unusual case of unilateral, chronic symptoms and signs of dry eye, and recurrent episodes of ocular irritation related to pinguecula, which were refractory to prior medical treatments, successfully treated with argon laser photocoagulation. Methods A 36-year-old man presented with an elevated yellowish mass on his conjunctiva in his left eye, which was associated with dry eye symptoms and general discomfort, such as “tightening sensation” and “stiffness”. On clinical assessment, the left eye revealed a mild conjunctival injection, a fluorescein break-up time (FBUT) of 3.5 s, an abnormal fluorescein staining, and a Schirmer I test of 5 mm. Optical coherence tomography (OCT) imaging evidenced a height at the most elevated point of the pinguecula of 740 µm. The patient underwent argon-laser photocoagulation. Results After 2 weeks postoperatively, no residual of pinguecula or focal injection of the conjunctiva was detected by slit-lamp biomicroscopy and there was a significant improvement of clinical symptoms and signs: Schirmer I test and FBUT increased to 12 mm and >10 s, respectively, and fluorescein staining was absent. OCT imaging revealed a smooth structure of conjunctival contour, with a height of 404 µm. According to an ex juvantibus line of reasoning, definitive diagnosis was pinguecula-related dry eye disease. Conclusion Based on the concept that tear film instability and inflammation are two key components of the pathogenesis of dry eye, we coined the term “pinguecula-related dry eye disease,” which can be successfully treated by a complete, accurate removal of the lesion with argon laser photocoagulation.

Simultaneous occlusion of three cilioretinal arteries following scleral buckling surgery under local anesthesia

Background Cilioretinal artery (CRA) occlusions are rare in young patients. In these cases, the most commonly associated causes are considered to be the same as those implicated in central retina artery occlusions, such as vasculitic processes, migraine, cardiac disorder, and coagulation abnormality. The aim of this article was to report for the first time the medical records and investigational results of an unusual case of simultaneous occlusion of three CRAs after scleral buckling surgery under local anesthesia. Methods A complete ophthalmic examination, including color fundus image, fundus fluorescein angiography, optical coherence tomography, visual field, as well as systemic and laboratory assessments, was performed. Results A case of contemporaneous blockage of three CRAs after ab externo surgery for retinal detachment in a 29-year-old Caucasian woman was reported. The interdisciplinary approach and the imaging results have allowed us the clinical definition of such a very rare case. Conclusion Here, we reported that optical coherence tomography is an indispensable tool to better delineate the pathological process and follow atrophic changes in the macula, especially in cases in which fundus fluorescein angiography and systemic tests may be poorly informative.

Rebound macular edema following oral acetazolamide therapy for juvenile X-linked retinoschisis in an Italian family

Background Juvenile X-linked retinoschisis (RS1, OMIM: 312700) is a hereditary vitreoretinal dystrophy characterized by bilateral foveal schisis and, in half of the patients, splitting through the nerve fiber layer in the peripheral retina. In the first decade of life, patients usually develop a decrease in visual acuity. Long-term visual outcomes can be poor due to the limited number of known successful treatments. Purpose The purposes of this study were to present, for the first time, a p.Arg197Cys missense mutation in the RS1 gene (OMIM: 300839) in a four-generation Italian family with RS1 and to examine the clinical response to the treatment with acetazolamide tablets alone or in combination with dorzolamide eye drops as assessed by spectral-domain optical coherence tomography (SD-OCT). Methods Eleven individuals, including two brothers with RS1 (patients 1 and 2), underwent a full medical history examination and a comprehensive ocular assessment that involved SD-OCT, fluorescein angiography, electroretinography and DNA analysis. Each RS1 patient received oral acetazolamide (375 mg daily) during the first three months. Thereafter, patient 1 continued only with dorzolamide eyedrops three times a day for a period of three months, while patient 2 spontaneously stopped both medications. Results Sequence analysis of the RS1 gene identified a hemizygous c.589C>T (p.Arg197Cys) missense mutation in exon 6, which has not been previously reported in an Italian family. A different response to the medical therapy was observed in the four eyes of the two affected brothers hemizygous for this abnormality. Of note, after acetazolamide interruption, a rebound effect on cystoid macular edema reduced the beneficial effects of the initial therapy for RS1 from p.Arg197Cys mutation. Indeed, a minimal rebound effect on cystoid macular edema, and an improvement in visual acuity, was observed in patient 1 during the six months of treatment. Conversely, in patient 2, an initial improvement in cystoid macular edema was not associated with visual acuity changes, followed by a marked rebound effect. Conclusion This study showed that the sequential use of acetazolamide tablets and dorzolamide eye drops should be considered and studied further as a possible treatment for macular edema and visual impairment in patients with RS1 from a hemizygous p.Arg197Cys mutation.