Paolo Nucci

In Vivo Confocal Evaluation of the Ocular Surface Morpho-Functional Unit in Dry Eye

Purpose To study, by a new, integrated, laser scanning confocal microscopy approach, the ocular surface morpho-functional unit in patients with primary Sjogren syndrome (SSI), non–Sjogren syndrome dry eye (non-SSDE), and meibomian gland disease (MGD). Methods Patients and age- and sex-matched control subjects (N = 60; 15 each) were consecutively enrolled in a prospective case-control study. Laser scanning confocal microscopy was used to obtain simultaneous optical sampling of the ocular surface components: cornea, bulbar and tarsal conjunctiva, MGs, and eyelid margin. Results For all superficial epithelia, except eyelid margins, there were reduced cell densities in each group compared with that in controls (p < 0.001). The lowest cell densities were in the SSI group (p < 0.001). Eyelid margin superficial cell density was decreased only in MGD (p < 0.001). Basal epithelial cell density at the corneal apex was increased in both SSI and non-SSDE compared with that in controls (p < 0.01). In the conjunctiva, it was decreased in each group compared with that in controls (p < 0.01). Subbasal dendritic cell density was significantly increased in both SSI and MGD compared with that in controls (p < 0.01). Conjunctival inflammatory cell density and MG inflammation were increased in each group compared with those in controls (p < 0.001), with the highest values in SSI. Subbasal nerve plexi had fewer fibers and higher bead density in each group compared with those in controls (p < 0.001). There was increased tortuosity in both SSI and MGD (p < 0.001). Patients with MGD had the lowest MG acinar density, the largest diameter of acini and acinar orifices, and the highest secretion reflectivity (p < 0.001). Conclusions Laser scanning confocal microscopy can provide an in vivo, noninvasive, high-resolution overview of the ocular surface morpho-funcional unit. This confocal integrated approach may be useful in both research and clinical settings.

Conservative management of congenital nasolacrimal duct obstruction

Fifty-nine children 1 to 24 months of age with congenital nasolacrimal duct obstruction (CNDO) were treated with local hydrostatic massage and antibiotic eye drops. Children 1 to 12 months of age showed a cure rate of 93.3%; only two of them underwent nasolacrimal probing. Children 13 to 24 months of age had a cure rate of 79.3%, and six underwent probing. The initial probings were successful in both age groups. Fifty-one children (86.4%) were thus spared nasolacrimal probing.

Compliance in antiamblyopia occlusion therapy

Abstract Antiamblyopia occlusion therapy relies on compliance. We retrospectively reviewed the charts of 496 amblyopic subjects. Measures of non‐compliance included patient reporting and patient records of broken appointments. Out of 496 subjects, 92 (18%) failed to follow the occlusion regimen. Compliance with treatment was analyzed by age group, refractive error and type of strabismus. The failure rate was 82.6% for the unilateral high myopia group and 37.5% for the monofixation syndrome group. The risk for non‐compliance appeared to be higher in the 1 to 2‐year‐old group (37%). The x2‐test showed the differences to be highly significant (P<0.0001). Children having lower initial visual acuity were also significantly less compliant (P<0.007). Several factors such as age, parental understanding, initial visual acuity and improvement rate seem to be involved in compliance.

Normal Exophthalmometric Values in Children

We used a Hertel exophthalmometer to measure the degree of ocular protrusion in 852 subjects who had no history of orbital trauma or disease, endocrine disease, severe myopia, buphthalmos, or craniofacial deformities. The subjects ranged in age from 3 to 10 years. No statistically significant difference was observed between boys and girls or between right and left eyes in each age group. The mean normal protrusion values ranged from 9.11 mm in the 3-year-old group to 11.67 mm in the 10-year-old group. The mean outer orbital margin distance ranged from 78.7 mm in the 3-year-old group to 89.1 mm in the 10-year-old group. The data obtained were tabulated to plot percentile distribution curves of normal exophthalmometric values and outer orbital margin distance in children. No subject had more than 2 mm of asymmetry between the eyes.

Photorefractive keratectomy for the treatment of purely refractive accommodative esotropia

Purpose: To evaluate the results of photorefractive keratectomy (PRK) for the treatment of young adult patients with purely refractive accommodative esotropia. Setting: Private practice and university hospital, Milan, Italy. Methods: The medical records of consecutive patients who had PRK for hyperopia associated with purely refractive esotropia were reviewed retrospectively. Preoperative and postoperative visual acuity, alignment, and sensory data were recorded and analyzed. Surgical methods and complications were reviewed. Results: Sixteen eyes of 8 patients were treated. The mean patient age at the time of treatment was 24.6 years (range 17 to 38 years). All patients were followed for 1 year. At the 1‐year follow‐up evaluation, the uncorrected visual acuity was 20/40 or better in all eyes. No patient lost a line of best spectacle‐corrected visual acuity. The mean spherical equivalent was −3.7 diopters (D) preoperatively and −0.7 D postoperatively. All patients were within ±0.37 D of emmetropia at the 1‐year evaluation. Preoperatively, the mean esotropic deviation was 10.75 prism diopters. Postoperatively, all patients were orthophoric without correction. Stereopsis was unaffected by PRK in all patients. There were no intraoperative or postoperative complications. Conclusion: Photorefractive keratectomy was an effective treatment for esotropia associated with mild to moderate hyperopia in young adults with purely refractive accommodative esotropia. These findings should not be widely applied to children with accommodative esotropia.

Spectral domain optical coherence tomography findings in patients with acute syphilitic posterior placoid chorioretinopathy.

Purpose: To describe the appearance of acute syphilitic posterior placoid chorioretinitis, a rare ocular manifestation of syphilis, on spectral domain optical coherence tomography (SD OCT) both before and after treatment. Methods: Ophthalmic examination and imaging studies of 30 eyes of 19 confirmed cases were analyzed both at the time of presentation and at each follow-up visit. Patients with SD OCT and fluorescein angiography at the time of presentation, and at least three documented follow-up visits after initiation of therapy, were included in the study. Standard treatment of neurosyphilis was given to each patient, including 4 million units of penicillin G administered intravenously every 4 hours for 14 days. Results: Fundus examination and imaging studies were consistent with previous reports and confirmed the diagnosis of acute syphilitic posterior placoid chorioretinitis. In 13 eyes (43.3%), baseline SD OCT scans were performed within 1 to 2 days of presentation and revealed a small amount of subretinal fluid, disruption of the inner segment/outer segment junction, and hyperreflective thickening of the retinal pigment epithelium (RPE). All 30 eyes were again scanned between Days 7 and 9 after presentation and revealed loss of the inner segment/outer segment and OS/RPE bands, and irregular hyperreflectivity of the RPE with prominent nodular elevations but without subretinal fluid. Early disruption of the external limiting membrane and punctate choroidal hyperreflectivity were seen in 1 of the 30 eyes (3.3%) and 14 of the 30 eyes (46.6%), respectively. Vision improved and the outer retinal abnormalities normalized in 28 of the 30 eyes (93.3%) after the treatment of neurosyphilis. The external limiting membrane, inner segment/outer segment band, and/or linear outer segment/RPE junction remained substantially abnormal despite treatment in 2 eyes left with 20/200 vision. Conclusion: Patients with acute syphilitic posterior placoid chorioretinitis show characteristic outer retinal abnormalities on SD OCT imaging, including disruption of the inner segment/outer segment band, nodular thickening of the RPE with loss of the linear outer segment/RPE junction, and, in some cases, loss of the external limiting membrane, accumulation of subretinal fluid, and punctate hyperreflectivity in the choroid. Vision improved and these abnormalities reversed after treatment of neurosyphilis in most of the patients. Persistently, poor vision despite treatment was associated with long-term loss or disruption of outer retinal anatomy on SD OCT.

The Aging Meibomian Gland: An In Vivo Confocal Study

PURPOSE To evaluate age-related Meibomian gland (MG) changes by in vivo laser scanning confocal microscopy (LSCM). METHODS Asymptomatic healthy subjects (n=100, age range 20-83 years) with an Ocular Surface Disease Index score of less than 13 were consecutively enrolled. Two additional groups, one composed of subjects under 40 years of age (n=12) and one composed of subjects over 65 years (n=12), were included without inclusion or exclusion criteria. All subjects underwent a full ocular surface evaluation, and one eye of each subject was examined by LSCM to quantify the lower lid MG acinar unit diameters and densities, orifice diameters, secretion reflectivity, interstices inhomogeneity, and acinar wall inhomogeneity. RESULTS In the asymptomatic population, MG density and diameter decreased with age (P<0.001 and P<0.01, respectively), and secretion reflectivity and inhomogeneity of acinar walls increased (P<0.001). For the under 40-year-old subjects and the over 65-year-old subjects included without any inclusion or exclusion criteria, acinar unit density decreased with age, and secretion reflectivity, and wall inhomogeneity increased (P<0.01). There was no significant difference between the mean acinar diameters of these two groups. CONCLUSIONS In vivo LSCM imaging of age-related MG changes showed the histologic features underlying the clinically observed MG dropout. Asymptomatic older subjects mainly showed signs of atrophic, nonobstructive, age-related MG dysfunction. Comparing volunteers with and without ocular surface symptoms, LSCM can provide important information regarding the boundary between physiologic and pathologic MG aging.

Corneal Confocal Microscopy in Dry Eye Treated with Corticosteroids.

Purpose To evaluate, by in vivo laser scanning confocal microscopy (LSCM), the corneal findings in moderate-to-severe dry eye patients before and after treatment with topical corticosteroid and to associate the confocal findings to the clinical response. Methods Fifty eyes of 50 patients with moderate-to-severe dry eye were included in this open-label, masked study. Exclusion criteria were any systemic or ocular condition (other than dry eye) and any systemic or topical treatment (except artificial tears), ongoing or performed in the previous 3 months, with known effect on the ocular surface. All patients were treated with loteprednol etabonate ophthalmic suspension 0.5% qid for 4 weeks. Baseline and follow-up (day 30 ± 2) visits included Ocular Surface Disease Index (OSDI) questionnaire, full eye examination, and central cornea LSCM. We compared data obtained before and after treatment and looked for associations between baseline data and steroid-induced changes. Based on the previously validated OSDI Minimal Clinically Important Difference, we reanalyzed the baseline findings comparing those patients clinically improved after steroids to patients not clinically improved after steroids. Results Ocular Surface Disease Index score and LSCM dendritic cell density (DCD) significantly decreased after treatment. Baseline DCD correlated with both OSDI and DCD steroid-related changes (r = −0.44, p < 0.05 and r = −0.70, p < 0.01, respectively; Spearman) and was significantly higher in patients clinically improved after steroids than in patients not clinically improved after steroids (164.1 ± 109.2 vs. 72.4 ± 45.5 cells/mm2, p < 0.01; independent samples t test). Conclusions Laser scanning confocal microscopy examination of DCD allows detection of treatment-related inflammation changes and shows previously unknown associations between confocal finding and symptoms improvement after treatment. These promising preliminary data suggest the need for future studies testing the predictive value of DCD for a clinical response to topical corticosteroids.

Inflammation in dry eye associated with rheumatoid arthritis: Cytokine and in vivo confocal microscopy study

The purpose of this research was to study ocular surface inflammation in relation to systemic disease activity in rheumatoid arthritis (RA) patients with or without secondary Sjögren’s syndrome (SSII and non-SSII respectively). The study was conducted in two phases. In phase I, 12 patients with active RA SSII and 12 with active RA non-SSII were consecutively enrolled. Each completed an Ocular Surface Disease Index (OSDI) questionnaire and underwent a full eye exam and in vivo confocal microscopy examination of the cornea. Tear fluid samples were collected in sponges and analyzed for IL-1α, -6, and -8, and TNF-α. When RA activity was suppressed by systemic treatment the patients entered phase II of the study in which all of the phase I examinations were repeated. In RA SSII patients, OSDI, fluorescein staining dendritic cell density, and concentrations of IL-1α and IL-6 decreased significantly (P < 0.01) between phases I and II. Tear breakup time scores increased significantly. For RA non-SSII patients, there were no significant differences between phases I and II. Differences in the clinical, cellular and cytokine responsiveness to systemic RA treatments show that the ocular surface pathology is dissimilar for RA SSII and RA non-SSII patients.

In-vivo confocal microscopy of the ocular surface: ocular allergy and dry eye.

Purpose of reviewTo summarize recent studies on in-vivo confocal microscopy (IVCM) findings in ocular allergy and dry eye disease (DED), highlighting the role of IVCM in the advancement of knowledge of these diseases. Recent findingsIVCM provided new data on ocular surface changes in both ocular allergy and DED. Corneal and conjunctival epithelial and inflammatory cells, corneal nerves, and Meibomian glands showed peculiar patterns of abnormalities, not easily discernable with current clinical exams in these two diseases and their subtypes. At present, small sample size of researches, and poor standardization and evidence of image analysis and interpretation are the most challenging issues. SummaryOcular allergy and DED are common and increasing healthcare problems, and need better understanding of pathogenesis and natural history, more reliable endpoints, and more tailored diagnostic and therapeutic approaches. IVCM allows quick, noninvasive, steady-state respectful examination of the ocular surface at cellular level to be performed and has potential to be used in the future as a biomarker and to contribute to optimize the tailored management of these diseases.