Dexamethasone/Netilmicin Eye Drops and Eye Gel for the Treatment of Ocular Inflammation After Micro-Incisional Vitreoretinal Surgery.

PURPOSE: To evaluate the effect of dexamethasone/netilmicin (dexa/net) fixed combination in the treatment of ocular inflammation after sutureless micro-incisional vitreoretinal surgery (MIVS). PATIENTS AND METHODS: This multicenter, open, randomized, active-controlled, parallel-group, clinical trial was run in 6 sites in Italy. Treatment started the day of surgery and continued 4 times daily for 14 days. Patients were 1:1 randomized to dexa/net (eyedrops solution and eye gel) or dexamethasone/tobramycin (dexa/tobra) eyedrops suspension and ointment. Viscous formulations (gel or ointment) were used alone during the early post-operative phase; afterwards, a combination of eye drops during daytime and viscous formulations at bedtime was adopted. The primary efficacy parameter evaluated was bulbar conjunctival hyperemia. Additional efficacy and safety parameters (palpebral conjunctival hyperemia, anterior chamber flare and cells, symptoms of ocular discomfort and ocular tolerance, adverse events and intraocular pressure) were also evaluated. Control visits were performed at day 1, day 4 and day 14 after surgery; the endpoint of the study was set at 14±2 days after surgery. RESULTS: A complete resolution of bulbar conjunctiva hyperaemia at the study end point was reached in 92.9% of patients treated with dexa/net and 75.0% of those treated with dexa/tobra (p=0.02, Fisher's exact test). No differences were observed between treatments for other efficacy parameters. Statistically significant differences in favour of dexa/net (p< 0.0001, ANOVA) were observed for most of subjective tolerance variables examined (blurred vision, foreign body sensation, stickiness, burning) starting day 1 after surgery when only the viscous formulations were used. No increase in intraocular pressure or adverse events was observed during the study. CONCLUSION: The combination dexa/net is safe and effective in the treatment of post-operative inflammation following sutureless MIVS. In particular, the use of eye gel formulation is characterized by a great tolerability.

The Ocular Surface in Medically Controlled Glaucoma: An In Vivo Confocal Study.

PURPOSE: To study clinical and in vivo laser scanning confocal microscopy (LSCM) ocular surface findings in stable, medically controlled primary open-angle glaucoma (MCPOAG) patients. METHODS: We recruited 100 consecutive patients with MCPOAG and 50 healthy controls. Patients had to have been treated with the same medical regimen without variation for the 18 months before enrollment and were excluded if there was a history of dry eye prior to glaucoma diagnosis. Each participant underwent ocular surface clinical and LSCM examination. RESULTS: In MCPOAG patients, subbasal nerve length and tortuosity and dendritic cell density were increased compared to controls (P < 0.01), but there were no clinical abnormalities. Patients treated with preserved drugs (n = 80) had reduced tear film breakup time (P < 0.05, ANOVA), and those preserved with benzalkonium chloride (n = 72) had reduced Schirmer test values (P < 0.001). Patients (n = 50) treated with two or more drugs had increased lissamine green conjunctival staining (P < 0.001, LSD post hoc test). Patients (n = 29) treated with three or more eye drops daily had decreased Schirmer test values. Laser scanning confocal microscopy showed subbasal changes related to preservatives, type and number of drugs, and number of eye drops. CONCLUSIONS: In stable MCPOAG patients without dry eye history, the ocular surface changes due to antiglaucoma medications are mostly subclinical. Active ingredients, preservatives, number of concomitant drugs, and number of eye drops instilled per day are all elements that can induce ocular surface changes. The clinical relevance of these changes remains to be determined.

Health-related quality of life in patients with primary open-angle glaucoma. An Italian multicentre observational study.

PURPOSE: As a progressive condition, glaucoma may impair health-related quality of life (HRQoL), due to vision loss and other factors. This study evaluated HRQoL in a cohort of patients treated for primary open-angle glaucoma (POAG) and assessed its association with clinical features. METHODS: This was an Italian, multicentre, cross-sectional, observational study with the subgroup of newly diagnosed patients with POAG prospectively followed up for one year. Patients with previous or new diagnosis (or strong clinical suspicion) of POAG aged >18 years were considered eligible. Information was collected on demographic characteristics, medical history, clinical presentation and POAG treatments. HRQoL was measured using the 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) and Glaucoma Symptom Scale (GSS). Subscale and total scores were obtained and a Pearson correlation coefficient between instruments' scores calculated. RESULTS: A total of 3227 patients were enrolled from 2012 to 2013 and 3169 were analysed. Mean age was 66.9 years. A total of 93.8% had a previous diagnosis (median duration: 8.0 years). Median values for mean deviation and pattern standard deviation were 3.9 and 3.6 dB, respectively. Mean scores on most subscales of the NEI-VFQ-25 exceeded 75.0 and mean GSS subscale scores ranged between 70.8 and 79.7 (with a total mean score of 74.8). HRQoL scores on both scales were significantly inversely associated with POAG severity. CONCLUSION: In this large sample of Italians treated for POAG, disease severity was limited and HRQoL scores were high. QoL decreased with advancing disease severity. These findings confirm the role of vision loss in impairing QoL in POAG, underlying the importance of timely detection and appropriate treatment.

Functional and Structural Abnormalities in Deferoxamine Retinopathy: A Review of the Literature.

Deferoxamine mesylate (DFO) is the most commonly used iron-chelating agent to treat transfusion-related hemosiderosis. Despite the clear advantages for the use of DFO, numerous DFO-related systemic toxicities have been reported in the literature, as well as sight-threatening ocular toxicity involving the retinal pigment epithelium (RPE). The damage to the RPE can lead to visual field defects, color-vision defects, abnormal electrophysiological tests, and permanent visual deterioration. The purpose of this review is to provide an updated summary of the ocular findings, including both functional and structural abnormalities, in DFO-treated patients. In particular, we pay particular attention to analyzing results of multimodal technologies for retinal imaging, which help ophthalmologists in the early diagnosis and correct management of DFO retinopathy. Fundus autofluorescence, for example, is not only useful for screening patients at high-risk of DFO retinopathy, but is also a prerequisite for identify specific high-risk patterns of RPE changes that are relevant for the prognosis of the disease. In addition, optical coherence tomography may have a clinical usefulness in detecting extent and location of different retinal changes in DFO retinopathy. Finally, this review wants to underline the need for universally approved guidelines for screening and followup of this particular disease.

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.

Longitudinal modifications of the Ozurdex intravitreal implant as imaged by SD-OCT.

PURPOSE: To describe in vivo longitudinal modifications of the Ozurdex intravitreal implant using spectral-domain optical coherence tomography (SD-OCT) over a 6-month period in an eye treated for retinal vein occlusion (RVO). METHODS: Case report. RESULTS: An 82-year-old woman with severe macular edema secondary to branch RVO received an Ozurdex intravitreal implant in the left eye. At day 1, SD-OCT showed that the implant was completely filled with highly reflective dexamethasone. At day 30, complete resolution of macular edema on SD-OCT was noted. At day 60, macular edema started to relapse; SD-OCT scans over the implant showed highly reflective borders that appeared irregular and focally retracted, while the majority of the internal drug had been washed out. At day 180, macular edema returned to baseline levels; SD-OCT scans over the implant showed that the device was contracted with almost complete absence of the internal lumen and drug. CONCLUSIONS: Using SD-OCT, we demonstrated that 60 days postinjection most dexamethasone had been released from the Ozurdex implant, which showed multiple irregularities. This was associated with recurrence of macular edema that became worse after 180 days, when there was no residual dexamethasone remaining in the shrunken implant. Low steady levels of the drug in the vitreous and lower biological activity in the retina after the 2-month high-dose release phase may explain why a large number of patients lose clinical improvement 60 days postinjection, as shown by pivotal clinical trials.

Choroidal granulomas visualized by enhanced depth imaging optical coherence tomography.

PURPOSE: To assess the visualization of choroidal granulomas (CG) by enhanced depth imaging optical coherence tomography (EDI-OCT) and to describe their EDI-OCT characteristics. METHODS: Combined indocyanine green (ICG) angiography and EDI-OCT images of 44 CG (sarcoid, tubercular, or Vogt-Koyanagi-Harada related) were reviewed. By ICG angiography, CG were classified as full thickness or partial thickness and as small or large. Two independent operators evaluated EDI-OCT scans over granulomas to record their characteristics (full thickness/partial thickness, shape, reflectivity, internal pattern, margins, and shadowing/increased transmission effect). The agreement between ICG angiography and EDI-OCT, the interobserver agreement, and the correlations between EDI-OCT features and lesion size or disease were studied. RESULTS: Enhanced depth imaging optical coherence tomography could visualize 100% of CG detected on ICG. Lesions resulted full thickness in 90.9% and 77.3% of the cases on ICG angiography and EDI-OCT, respectively (K = 0.5). All CG were more homogeneous and showed increased transmission of the optical coherence tomography signal as compared with the surrounding choroid. Choroidal granulomas angiographic size influenced lesions characteristics on EDI-OCT. Large granulomas were more likely to be full thickness, round shaped, with defined margins, lower reflective than the surrounding structures, and with internal homogenous pattern. The type of disease significantly influenced CG shape and pattern. Most of tubercular-related lesions showed lobulated shape and nonhomogeneous internal pattern. CONCLUSION: Enhanced depth imaging optical coherence tomography is suitable to visualize CG and to describe their characteristics. Choroidal granulomas size and disease influence lesions appearance on EDI-OCT. Increased transmission effect could be helpful for CG identification.

Choroidal findings in dome-shaped macula in highly myopic eyes: a longitudinal study.

PURPOSE: To describe choroidal findings in dome-shaped macula associated with high myopia using fluorescein angiography (FA), indocyanine green angiography (ICGA), and spectral-domain optical coherence tomography (SD OCT), and to elucidate the mechanism and natural course of serous retinal detachment (RD) associated with dome-shaped macula. DESIGN: Retrospective, observational case series. METHODS: We reviewed longitudinal imaging results of 52 highly myopic eyes with dome-shaped macula. Changes on FA and ICGA were assessed. Retinal, choroidal, and scleral thicknesses and bulge height were measured on SD OCT. RESULTS: Serous RD was the most common abnormality associated with dome-shaped macula, detected by SD OCT in 44% of the cases with no associated choroidal neovascularization. Significant differences in the proportion of eyes with pinpoint leakage on FA (P < .001), punctate hypercyanescence on ICGA (P < .001), and pigment epithelium detachment on SD OCT (P < .001) were noted inside the inward bulge of the staphyloma between eyes with and without serous RD. Serous RD was not associated with hyperpermeability areas on ICGA. Eyes with serous RD had thicker choroid (P = .004) and tended to have thicker sclera (P = .067) and greater bulge height (P = .079). Choroidal thickness, scleral thickness, and bulge height were positively correlated (P < .01). All eyes presented a fluctuating course of serous RD during follow-up. Worsening of serous RD was associated with appearance of new punctate hypercyanescent spots on ICGA and leaking points on FA (P < .001 and P = .016, respectively). CONCLUSION: Serous RD in dome-shaped macula was likely caused by choroidal vascular changes, similar to central serous chorioretinopathy, but specifically confined in the inward bulge of the staphyloma and secondary to excessive scleral thickening. Serous retinal detachment showed fluctuating changes over time, with alternating active and inactive stages. Angiographic findings in dome-shaped macula suggest the choroid as a target for possible treatment strategies.

Evaluation of a novel eyelid-warming device in meibomian gland dysfunction unresponsive to traditional warm compress treatment: an in vivo confocal study.

The purpose of the study was to evaluate the efficacy and safety of wet chamber warming goggles (Blephasteam(®)) in patients with meibomian gland dysfunction (MGD) unresponsive to warm compress treatment. We consecutively enrolled 50 adult patients with low-delivery, non-cicatricial, MGD, and we instructed them to apply warm compresses twice a day for 10 min for 3 weeks and to use Blephasteam(®) (Laboratoires Thea, Clermont-Ferrand, France) twice a day for 10 min for the following 3 weeks. We considered "not-responders" to warm compress treatment the patients who showed no clinically significant Ocular Surface Disease Index (OSDI) improvement after the first 3 weeks. Clinical and in vivo confocal outcome measures were assessed in the worst eye (lower BUT) at baseline, after 3 weeks, and after 6 weeks. Eighteen/50 patients were not-responders to warm compress treatment. These patients, after 3 weeks of treatment with Blephasteam(®), showed significant improvement of OSDI score (36.4 ± 15.8 vs 20.2 ± 12.4; P < 0.05, paired samples t test), increased BUT (3.4 ± 1.6 vs 7.6 ± 2.7; P < 0.05), and decreased acinar diameter and area (98.4 ± 18.6 vs 64.5 ± 14.4 and 8,037 ± 1,411 vs 5,532 ± 1,172, respectively; P < 0.05). Neither warm compresses nor Blephasteam(®) determined adverse responses. In conclusion, eyelid warming is the mainstay of the clinical treatment of MGD and its poor results may be often due to lack of compliance and standardization. Blephasteam(®) wet chamber warming goggles are a promising alternative to classical warm compress treatment, potentially able to improve the effectiveness of the "warming approach."

Multimodal imaging in deferoxamine retinopathy.

PURPOSE: To describe macular lesions in patients with deferoxamine (DFO) retinopathy, and to follow their clinical course using multimodal imaging. METHODS: The authors retrospectively reviewed charts and multimodal imaging of 20 patients with ß-thalassemia diagnosed with DFO retinopathy (40 eyes) after a minimum of 10 years of DFO treatment. Imaging included fundus photography, near-infrared reflectance and fundus autofluorescence imaging on confocal laser scanning ophthalmoscope, and spectral domain optical coherence tomography. RESULTS: Mean age of the 20 patients was 45 years, and mean duration of subcutaneous DFO therapy was 32 years (range, 20-52 years). Ten patients (50%) showed different types of pattern dystrophy-like fundus changes, including butterfly shaped-like (n = 3), fundus flavimaculatus-like (n = 3), fundus pulverulentus-like (n = 3), and vitelliform-like (n = 1) changes. Ten patients (50%) presented only minimal changes in the macula; these patients were significantly younger than patients presenting other patterns (P = 0.023). Confocal laser scanning ophthalmoscope and spectral domain optical coherence tomography showed that these abnormalities were more diverse and widespread than expected by ophthalmoscopy. Abnormal fundus autofluorescence and/or near-infrared reflectance signals corresponded to accumulation of material located within the outer retina or in the Bruch membrane-retinal pigment epithelium (RPE) complex on spectral domain optical coherence tomography. Follow-up examinations during a 40-month period revealed progressive development of RPE atrophy in areas of pattern dystrophy-like changes. CONCLUSION: DFO retinopathy included a variety of pattern dystrophy-like changes or minimal changes affecting the RPE-Bruch membrane-photoreceptor complex. Multimodal imaging demonstrated that fundus changes were more diverse and widespread than expected from ophthalmoscopy. Consistently with previous histologic description of DFO retinopathy, multimodal imaging confirmed that photoreceptor outer-derived retinoids, various fluorophores, and RPE displacement or clumping are involved in DFO retinopathy, finally leading to frank RPE atrophy in most cases of pattern dystrophy-like changes.

Therapeutic outcomes of high-dose intravenous steroids in the treatment of dysthyroid optic neuropathy.

BACKGROUND: While pulsed intravenous methylprednisolone (iv-MP) has been shown to be effective and well tolerated in moderate to severe Graves' orbitopathy (GO), limited data are available on dysthyroid optic neuropathy (DON). The objective of this retrospective study was to investigate the efficacy of iv-MP in the treatment of DON and to seek parameters predictive of response. METHODS: Twenty-four DON patients (40 eyes) treated with iv-MP from 2007 to 2012 were included in the study. Concurrent neurological or ophthalmologic diseases or signs of corneal exposure were considered as exclusion criteria. Iv-MP was administered daily for three consecutive days and repeated the following week. At six months, eyes not requiring surgery to preserve visual function were considered as responsive to treatment. Visual acuity, color sensitivity, visual field, and optic discs were analyzed at two and four weeks, and at 3, 6, and 12 months after treatment. Activity of GO was graded using a clinical activity score (CAS). Visual and clinical characteristics of the eyes responsive to iv-MP were studied by comparison to those of nonresponsive eyes. RESULTS: At six months, 17 of 40 (42.5%) eyes had complete visual recovery and were spared from surgical decompression. At two weeks, visual acuity, color sensitivity, and visual field improved significantly in almost all eyes, but GO inactivated (CAS<4) only in the eyes that permanently responded to iv-MP (p<0.01). The CAS at two weeks was a good predictor of response (cutoff ≥4; 66.7% sensitivity, 76.9% specificity). Optic disc swelling at diagnosis was highly predictive for unresponsiveness to iv-MP (34% sensitivity, 100% specificity). At baseline, high CAS (cutoff >5; 40.2% sensitivity, 94.1% specificity) and severely altered visual field mean defect (cutoff ≤6.31 dB; 73.9% sensitivity, 58.8% specificity) were associated with unresponsiveness to steroids. No major side effects were observed. CONCLUSIONS: High-dose iv-MP was effective in permanently restoring visual function in about 40% of the eyes treated. When successful, it generally induced inactivation of the orbital disease within two weeks and normalization of visual function within one month. The presence of optic disc swelling at diagnosis and persistent active disease at two weeks were good predictors of unresponsiveness to steroids.

The spectrum of ocular alterations in patients with ß-thalassemia syndromes suggests a pathology similar to pseudoxanthoma elasticum.

PURPOSE: To determine the prevalence and spectrum of ocular fundus abnormalities in patients with ß-thalassemia and to investigate risk factors for their development. DESIGN: Cross-sectional, observational study. PARTICIPANTS: A total of 255 patients with ß-thalassemia major (TM) and ß-thalassemia intermedia (TI) were consecutively recruited and investigated. METHODS: Patients underwent best correct visual acuity, indirect ophthalmoscopy, and fundus photography, including fundus autofluorescence (FAF) and near-infrared reflectance imaging using a confocal scanning laser ophthalmoscope (cSLO). Hematologic parameters were determined, including mean ferritin levels, aspartate amino transferase, alanine amino transferase, calcium, pre-transfusion hemoglobin, history of splenectomy, and liver iron concentration. Factors associated with the ocular phenotype were assessed using logistic regression. MAIN OUTCOME MEASURES: Ocular phenotype as determined by clinical examination and used multimodal imaging. RESULTS: A total of 153 patients (60.0%) affected by TM and 102 patients (40.0%) affected by TI participated, of whom 216 (84.7%) were receiving iron-chelating therapy. Ocular fundus abnormalities characteristic of pseudoxanthoma elasticum (PXE) were detected by cSLO in 70 of 255 patients (27.8%) and included peau d'orange (19.6%), angioid streaks (12.9%), pattern dystrophy-like changes (7.5%), and optic disc drusen (2.0%). Pseudoxanthoma elasticum-like changes were more frequent in patients with TI (P<0.001). Patients with PXE-like fundus changes were older than patients without these fundus changes (P<0.001). In both patients with TI and TM, age (P = 0.001) and splenectomy (P = 0.001) had the strongest association with presence of PXE-like fundus changes in multivariate analyses. A total of 43 of 255 patients (16.9%) showed increased retinal vascular tortuosity independently of the PXE-like fundus changes, which was associated with aspartate amino transferase (P = 0.036), hemoglobin (P = 0.008), and ferritin levels (P = 0.005). CONCLUSIONS: Pseudoxanthoma elasticum-like fundus changes are a frequent finding in patients with ß-thalassemia. In TI, these changes increase with duration or severity of the disease. This particular ocular phenotype suggests an ocular pathology similar to PXE. Retinal vascular tortuosity may be an additional disease manifestation independent of the PXE-like syndrome. Patients with long-standing disease requiring iron-chelating treatment and a history of splenectomy need regular ophthalmic checkups because they are at risk of developing PXE-like fundus changes and potentially of subsequent choroidal neovascularization.

The cornea in classic type Ehlers-Danlos syndrome: macro- and microstructural changes.

PURPOSE: To analyze in vivo corneal morphology and ultrastructural features in patients with classic Ehlers-Danlos syndrome (EDS). METHODS: Fifty patients with classic EDS and 50 age- and sex-matched control subjects were studied. A clinical evaluation was made with the Ocular Surface Disease Index (OSDI) questionnaire and a complete ophthalmic examination, including assessment of the best-corrected visual acuity and refraction, slit-lamp biomicroscopy, tear break-up time, intraocular pressure, Schirmer test without topical anesthesia, and corneal diameter. Scheimpflug camera topography and in vivo confocal microscopy (IVCM) were used to investigate corneal morphology and corneal ultrastructural features respectively. RESULTS: Classic EDS patients, compared to controls, had thinner and steeper corneas (P < 0.001 and P < 0.05, respectively; independent samples t-test). IVCM showed thinner stromas, lower keratocyte densities (P < 0.001), increased applanation-related stromal folds (P < 0.001; Mann-Whitney U test), and increased endothelial hyperreflective dots (P < 0.05) in these patients. The study group also had increased symptoms (OSDI score: P < 0.01, independent samples t-test) and signs (tear break-up time and Schirmer test: P < 0.001 and P < 0.05, respectively) of tear film dysfunction. CONCLUSIONS: Patients with classic EDS had macro- and microstructural changes of the cornea, which is a target tissue of the disease. These findings should be considered to optimize clinical management of these patients and to evaluate the opportunity of adding ocular findings to the classic EDS diagnostic criteria.

Choroidal volume variations during childhood.

PURPOSE: We analyzed choroidal volume (CV) variations during childhood using enhanced depth imaging optical coherence tomography, and evaluated its association with age, axial length (AXL), sex, weight, and height. METHODS: Imaging studies of the right eyes of 52 healthy children were reviewed and included in this study. Subjects underwent a complete ocular examination and AXL measurement, as well as a raster macular scan using the Heidelberg Spectralis device. The choroid was segmented manually. RESULTS: Subjects included 21 males and 31 females, with mean age of 9 years (range, 2-17 years) and mean AXL of 22.8 ± 0.98 mm. Mean CV was 0.263 ± 0.068 mm(3) for the foveal circle and 8.545 ± 1.822 mm(3) for the total Early Treatment of Diabetic Retinopathy Study (ETDRS) grid. The CV of the nasal quadrant was significantly lower than all others (P < 0.001). Total and foveal CV showed significant negative correlation with AXL after adjustment for age (P < 0.001), and significant positive correlation with age after adjustment for AXL (P < 0.001). Total CV was correlated significantly with sex after adjusting for AXL (P = 0.01), while no correlations were found between total CV and height or weight. The CV increased by 0.214 mm(3) (2.5%) for every year, and decreased by 1.0 mm(3) (11.7%) for every millimeter of axial length. Regression analysis confirmed a trend of higher CV in females than in males (P = 0.056). CONCLUSIONS: The CV increases with age during childhood, but decreases with AXL. This finding supports the hypothesis that the choroid grows progressively during childhood. Intersexual differences of CV also may be present.

Accuracy of the Heidelberg Spectralis in the alignment between near-infrared image and tomographic scan in a model eye: a multicenter study.

PURPOSE: To evaluate temporal changes and predictors of accuracy in the alignment between simultaneous near-infrared image and optical coherence tomography (OCT) scan on the Heidelberg Spectralis using a model eye. DESIGN: Laboratory investigation. METHODS: After calibrating the device, 6 sites performed weekly testing of the alignment for 12 weeks using a model eye. The maximum error was compared with multiple variables to evaluate predictors of inaccurate alignment. Variables included the number of weekly scanned patients, total number of OCT scans and B-scans performed, room temperature and its variation, and working time of the scanning laser. A 4-week extension study was subsequently performed to analyze short-term changes in the alignment. RESULTS: The average maximum error in the alignment was 15 ± 6 µm; the greatest error was 35 µm. The error increased significantly at week 1 (P = .01), specifically after the second imaging study (P < .05); reached a maximum after the eighth patient (P < .001); and then varied randomly over time. Predictors for inaccurate alignment were temperature variation and scans per patient (P < .001). For each 1 unit of increase in temperature variation, the estimated increase in maximum error was 1.26 µm. For the average number of scans per patient, each increase of 1 unit increased the error by 0.34 µm. CONCLUSION: Overall, the accuracy of the Heidelberg Spectralis was excellent. The greatest error happened in the first week after calibration, and specifically after the second imaging study. To improve the accuracy, room temperature should be kept stable and unnecessary scans should be avoided. The alignment of the device does not need to be checked on a regular basis in the clinical setting, but it should be checked after every other patient for more precise research purposes.

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.

Purtscher-like Retinopathy in Septicemic Disseminated Intravascular Coagulation Associated with Nephrotic Syndrome.

PURPOSE: To describe a case of severe Purtscher-like retinopathy during an episode of septicemic diffused intravascular coagulation (DIC) in a child with severe nephrotic syndrome. METHODS: Case report. RESULTS: A 5-year-old girl with a history of steroid-sensitive nephrotic syndrome was admitted for worsening symptoms of the systemic disease. Laboratory studies revealed evidence of DIC during an episode of septicemia. Ten days later, she had a sudden and severe bilateral visual loss. Her visual acuity was hand motion in either eye. Fundus examination showed ischemic retinal whitening and retinal hemorrhages. Fluorescein angiography revealed obstruction of arterioles and venules at the posterior pole. Three weeks later, ischemic retinal blanching and hemorrhages resolved in both eyes; visual acuity improved to 20/250 and 20/200 in right and left eye, respectively. No further functional improvement was noted after 3 months, due to diffuse thinning of the inner retina architecture as shown by optical coherence tomography. CONCLUSIONS: Purtscher-like retinopathy can occur in patients with septicemic DIC and nephrotic syndrome.

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-functional unit. This confocal integrated approach may be useful in both research and clinical settings.

A quantitative method for assessing the degree of axial proptosis in relation to orbital tissue involvement in Graves' orbitopathy.

PURPOSE: To define a method of quantifying axial proptosis in patients with Graves' orbitopathy (GO) and to validate a score that correlates with the orbital involvement and helps determine the degree of proptosis correction for elective orbital decompression. DESIGN: Retrospective, case series. PARTICIPANTS: The study included 50 patients (group A) and 29 control subjects who underwent orbital computed tomography (CT). The method was then validated in another group of 21 patients with GO (group B). METHODS: The orbital area (OA) was measured manually on the central axial section of the CT scan at a level where the lens is visualized. The OA intersects the projection of the globe and delimitates the chord of an arch (globe chord [OC]). The area of the circular sector under the chord (CA) represents the portion of the globe within the orbit. MAIN OUTCOME MEASURES: A CA-to-OA ratio was calculated to reduce the error due to variability of the measurements and to perform correlations with some of the clinical parameters of GO. RESULTS: Measurement error was low (<2%). We did not observe significant differences in the mean OA of patients with GO (783.6 ± 12.1 mm(2)) and controls (758.5 ± 20.4 mm(2); P = not significant). The OC value in patients with GO was 130.2 ± 11.5 mm(2), significantly lower than in controls (281.8 ± 9.7 mm(2); P<0.0001). The CA-to-OA ratio also was lower in patients with GO than in controls (0.16 ± 0.01 vs. 0.38 ± 0.01; P<0.0001). A significant correlation was found in patients with GO between the CA-to-OA ratio and proptosis (P<0.001), lid fissure (P = 0.004), and intraocular pressure (P<0.001). In group B, the CA-to-OA ratio was 0.18 ± 0.02, significantly different from that of controls (P<0.0001) and inversely correlated with proptosis (P<0.0001) and lid fissure (P<0.045). CONCLUSIONS: By measuring the CA-to-OA ratio, we were able to quantify the degree of axial proptosis in patients with GO. The significant correlation of CA/OA with some orbital parameters confirms that this parameter also may be used as a measure of orbital involvement in GO. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.