In vivo confocal microscopy morphometric analysis of corneal subbasal nerve plexus in dry eye disease using newly developed fully automated system.

PURPOSE: To evaluate in vivo confocal microscopy (IVCM) features of corneal subbasal nerve plexus (SNP) in the setting of dry eye disease (DED) using fully automated software "ACCMetrics," and to further investigate its diagnostic performance in discriminating DED patients. METHODS: IVCM exams of SNP in DED patients and matched control subjects were performed using Heidelberg Retina Tomograph with the Rostock Cornea Module. The following parameters were obtained with ACCMetrics: corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD), corneal nerve fiber length (CNFL), corneal nerve total branch density (CTBD), corneal nerve fiber area (CNFA), corneal nerve fiber width (CNFW), and corneal nerve fractal dimension (CNFrD). The Mann-Whitney U test was used to compare variables. Receiver operating characteristic curves with calculations of the area under the curve (AUC) were used to describe the accuracy of IVCM parameters for discriminating DED patients from controls. RESULTS: Thirty-nine DED patients and 30 control subjects were included. Significantly, lower values of CNFD, CNBD, and CNFL and higher value of CNFW were found in DED patients compared to controls (respectively, 20.5 ± 8.7 vs 25.4 ± 6.7 n/mm2; 25.6 ± 20.1 vs 37.6 ± 21.5 n/mm2; 12.6 ± 4.4 vs 14.5 ± 2.9 mm/mm2; 0.021 ± 0.001 vs 0.019 ± 0.001 mm/mm2; always p < 0.024). CNFW value had the highest diagnostic power in discriminating DED patients (AUC = 0.828). When the diagnosis of DED was made based on either CNFW or CNBD, the sensitivity was 97.4% and the specificity 46.7%. CONCLUSIONS: The software ACCMetrics was able to rapidly detect SNP alterations occurring in the setting of DED and showed good diagnostic performance in discriminating DED patients.

Ultrasound Cyclo-Plasty in Patients with Glaucoma: 1-Year Results from a Multicentre Prospective Study.

PURPOSE: The aim of this study was to evaluate the safety and efficacy of ultrasound cyclo-plasty (UCP) for reducing intraocular pressure (IOP) in patients with glaucoma. METHODS: This is a multicentre prospective study conducted in 3 Italian glaucoma centres. UCP was performed by EyeOP1, which delivers ultrasound beams using 6 piezoelectric transducers activated for 4/6 s (first generation) or 8 s (second generation). Primary outcomes were the mean IOP reduction and the rates of success after 1 year. Secondary outcomes were the mean IOP reduction at each follow-up, and the reduction of the number of hypotensive medications. RESULTS: In total, 49 eyes from 47 patients were treated. One year postoperatively, the mean IOP had decreased from 27.7 ± 9.2 to 19.8 ± 6.9 mm Hg (p < 0.001), and the mean number of hypotensive drops and tablets had decreased from 3.2 and 0.5 to 2.3 and 0.2, respectively (p < 0.05). Postoperative IOP reduction was significantly related to preoperative IOP (r2 = 0.5034; p < 0.0001). Second-generation probes determined a significantly higher IOP reduction (p < 0.05). Qualified success was achieved in 25 eyes (51.1%) and complete success in 21 (42.9%), while failure was recorded in 12 (24.5%). CONCLUSIONS: UCP is safe and effective for reducing IOP. The procedure determines a greater IOP reduction in patients with higher preoperative IOP. Second-generation probes improve outcomes without detrimental effects on safety.

Blood derived eye drops for the treatment of cornea and ocular surface diseases.

The use of blood derived eye drops for the treatment of ocular surface disorders has become increasingly popular in recent years. The mechanism of action is the stimulation of cellular proliferation and migration by supplying an active mixture of growth factors and cytokines at the ocular surface, thus mimicking the function of the lacking natural tears. Blood derived eye drops have been used in the last decades for the treatment of a variety of ocular surface diseases, including mainly dry eye disease, persistent corneal epithelial defect, corneal ulcer, ocular surface burn, recurrent corneal erosion and limbal stem-cell deficiency. Among overall blood derived eye drops, both autologous (from the patients themselves) and homologous (from donors) products exist, with different advantages and disadvantages. Autologous serum, obtained from the patient's own peripheral blood, is the first introduced and most commonly used product. Despite several randomized clinical trials showed its safety and efficacy, a recent Cochraine meta-analysis failed to show significant results due to low evidence. Homologous sources including allogeneic serum obtained from healthy donors, and umbilical cord blood serum collected at the time of delivery, are efficient alternatives, especially when autologous serum therapy is contraindicated or not appropriate. Platelet-derived eye drops are prepared and used in various but poor standardized preparations, namely platelet-rich plasma, plasma rich in growth factors, and platelet lysate. Future perspectives of blood-derived products include the introduction of tailored eye drops, screened for the proper content of growth factors and cytokines according to each patient and ocular surface disease.

Steroid intra-trochlear injection for the treatment of acquired Brown syndrome secondary to trochleitis.

PURPOSE: To evaluate the outcomes of early intra-trochlear steroid injections in patients with acquired Brown syndrome secondary to trochleitis (ABSST). METHODS: Retrospective analysis from medical charts of patients diagnosed as affected by unilateral ABSST from January 2008 to June 2015, and treated according to our Institution protocol: intra-trochlear injection of 1ml of triamcinolone acetonide 40 mg/ml is performed under sterile conditions. In cases of no resolution/improvement within 1 month, further monthly injections are performed up to a maximum number of three. Non-responder patients after three injections undergo recession of the superior oblique muscle. RESULTS: Thirteen patients were diagnosed as affected by unilateral ABSST, and were included in the analysis (seven F, six M; median age at diagnosis 30.38 ± 25.56 years). The mean time interval from ABSST diagnosis to the first steroid injection was 7.84 ± 5.40 days (range 2-17). After a median number of 1.30 injections per patient, 11 patients (84.6% of the total) showed complete remission of symptoms and signs within 22.45 ± 13.85 days after the first injection. None of these responder patients referred to diplopia in primary gaze after injections. The remaining two non-responder patients after three injections underwent superior oblique muscle recession of 8.0 mm. CONCLUSIONS: Early intra-trochlear steroid injections are effective in patients with acquired Brown syndrome secondary to trochleitis, leading to a complete recovery of signs and symptoms in the majority of treated patients. Surgical treatment should be limited only to patients non-responding to serial steroid injections.

Incidence rates of surgically treated rhegmatogenous retinal detachment among manual workers, non-manual workers and housewives in Tuscany, Italy.

PURPOSE: Candidate risk factors for idiopathic rhegmatogenous retinal detachment (RRD) include heavy manual handling (requiring Valsalva's maneuver). We assessed incidence rates of surgically treated idiopathic RRD among manual workers, non-manual workers and housewives resident in Tuscany, Italy. METHODS: We retrieved all hospital discharge records bearing a principal diagnosis corresponding to RRD coupled with retinal surgery for any resident of Tuscany during 1997-2009. After elimination of repeated admissions and patients with coexistent, associated conditions (including recent trauma), subjects aged 25-59 years were classified as manual workers, non-manual workers or housewives. Population data were extracted from the 2001 census. RESULTS: We identified 1,946 eligible cases (1,142 men). Among men, manual workers experienced a 1.8-fold higher age-standardized rate per 100,000 person-years than non-manual workers [17.4 (95 % confidence interval (CI) 16.1-18.7) vs. 9.8 (95 % CI 8.8-10.8)]. Age-standardized rates among women were 1.9-fold higher for manual workers [11.1 (95 % CI 9.8-12.3)] and 1.7-fold higher for housewives [9.5 (95 % CI 8.3-10.8)] than in non-manual workers [5.7 (95 % CI 4.8-6.6)]. CONCLUSIONS: This large population-based study suggests that manual workers are affected by idiopathic RRD requiring surgical treatment more often than non-manual workers. The higher rates of surgically treated RRD experienced by manual workers are in accord with the hypothesis that heavy manual handling may have a causal role.

Diagnostic performance of a tear protein panel in early dry eye.

PURPOSE: To evaluate the tear protein pattern in patients with recent subjective symptoms of dry eye (DE) and with poor distinctive DE clinical signs. METHODS: One hundred sixty patients suspected of suffering from mild to moderate DE according to the Dry Eye Workshop (DEWS report 2007) severity grade and 45 matched normal volunteers were included in the study. Subjective symptom score (Ocular Surface Disease index score), Schirmer test I, tear film break-up time, cornea and conjunctiva staining (National Eye Institute score); and tear protein analysis were performed. Statistical evaluation of data was performed with Mann-Whitney unpaired and Student t tests, (significance p<0.05). Correlations between variables were evaluated by using Pearson's (r) or Spearman's (ρ) correlation coefficients. Thresholds were selected from receiver operating curves; sensitivity, specificity, likelihood ratio (LR+), and positive predictive values were calculated for each protein. The combination of variables was carried out by univariate analysis, representing the best combination of tests for early DE diagnosis. RESULTS: TOTAL PROTEIN CONTENT (TP) AND THE FOLLOWING PROTEINS WERE RECOGNIZED IN ALL SAMPLES: lysozyme-C (LYS-C), lactoferrin (LACTO), tear lipocalin 1 (LIPOC-1), zinc-alpha-2-glycoprotein (ZAG-2), transferrin (TRANSF), and exudated serum albumin (ALB). A statistically significant decrease was demonstrated between normal subjects and patients with DE (mg/ml, mean±SD) for TP (9.89±2.28 versus 6.44±2.1), LYS-C (3.06±1.07 versus 2.15±0.78), LIPOC-1 (1.71±0.52 versus 0.98±0.5), ZAG-2 (0.43±0.24 versus 0.25±0.2), TRANSF (0.9±0.6 versus 0.33±0.3), and LACTO (2.11±0.74 versus 1.47±0.76), while an increase was found for ALB (0.21±0.5 versus 0.94±1.28). LIPOC-1 and ZAG-2 were strongly correlated to tear film break-up time. The proteins were related to the DEWS severity grade. Changes in each protein were a better predictor of early DE than were clinical variables; TP, LIPOC-1, and ALB exhibited the highest diagnostic performance either alone (LR+ 16.7, 12.3, 4.7, respectively) or when combined in a univariate analysis (LR+: 41.8, positive predictive value: 99.9). CONCLUSIONS: Our results demonstrated in tears from patients with early DE a significant reduction in tear protein content as a whole, associated with a decrease in proteins with antibacterial and protective functions. A decrease in proteins with lipid binding properties and an increase in inflammatory-related proteins were also shown. Changes in the abundance of a panel of tear proteins with divergent functions was found to better diagnose early DE than did conventional clinical tests.

Aqueous flare and choroidal thickness in patients with chronic hepatitis C virus infection: a pilot study.

PURPOSE: To investigate the status of the blood-aqueous barrier and to evaluate the subfoveal choroidal thickness (SCT) in patients with asymptomatic untreated chronic hepatitis C virus (HCV) infection without any anterior or posterior ocular involvement and to search for possible correlations. DESIGN: Observational case-control study. PARTICIPANTS AND CONTROLS: A total of 80 eyes of 20 HCV-positive patients (male-to-female ratio, 12:8; mean age, 46.9±7.23 years) and 20 healthy controls (male-to-female ratio, 10:10; mean age, 48.2±8.71 years) were examined. METHODS: Participants underwent a complete ophthalmologic examination. Aqueous flare was quantified objectively by using the noninvasive laser flare cell meter FC-500 (Kowa Company Ltd, Tokyo, Japan), whereas SCT was evaluated by using enhanced depth imaging optical coherence tomography (Spectralis OCT; Heidelberg Engineering GmbH, Heidelberg, Germany). A Wilcoxon rank-sum test was performed to compare ocular findings between HCV patients and controls, and correlations were assessed by using the Spearman rank test. MAIN OUTCOME MEASURES: Retinal and choroidal thickness and anterior chamber inflammation of HCV patients and healthy controls. RESULTS: Patients with HCV showed significantly higher aqueous flare values (8.37±2.25 photon counts/ms vs. 4.56±1.45 photon counts/ms; P<0.0001) and a significantly increased SCT (362.7±46.5 µm vs. 320.25±32.82 µm; P<0.0001) than healthy controls. Moreover, subjects with liver fibrosis had higher flare values than those with no significant hepatic fibrosis (9.62±1.99 photon counts/ms vs. 6.97±2.19 photon counts/ms; P = 0.0003) and thicker choroids (379.15±44.75 µm vs. 346.3±43.27 µm; P = 0.024). Statistical analysis revealed that there was a positive correlation between aqueous flare values and SCT in HCV patients (r = 0.69; P<0.0001) and between flare and the degree of liver fibrosis (r = 0.67; P = 0.0001). CONCLUSIONS: This study showed that impairment of the blood-aqueous barrier and thickened choroids are features of asymptomatic HCV patients, and that choroidal thickness increases as the degree of subclinical inflammation of the anterior chamber increases. Patients with significant liver fibrosis have the highest flare values and the thickest choroids.

Astigmatism in patients with idiopathic congenital nystagmus.

PURPOSE: To evaluate the association between astigmatism and idiopathic congenital nystagmus (ICN) in infantile nystagmus syndrome (INS). MATERIALS AND METHODS: We analysed refractive errors in a cohort of 488 consecutive patients with ICN (group A) and further compared the results obtained with those of 488 age-matched controls with no nystagmus (group B). Only the worst eye was considered for statistical analysis. All patients were stratified into the following age groups: 1 to 4 years (age group 1); 5 to 12 years (age group 2); and 13 years to 57 years (age group 3) (mean age: 29). RESULTS: Three hundred and seventy patients (69.7 %) in group A and 269 patients (55,12 %) in group B had refractive errors. The types of refractive errors observed were: myopia, hyperopia (>0.50 dioptres) and astigmatism (>1.25 dioptres). Results in group A were as follows: 319 patients (65.37 %) were astigmatic, 34 (6.97 %) were hyperopic, and 17 (3.48 %) were myopic. Mean right-eye astigmatism was 2.72 dioptres, and mean left-eye astigmatism was 2.69 dioptres. Results in group B were as follows: 56 (11.47 %) were astigmatic, 165 (33.81) were hyperopic, and 48 (9.84) were myopic. Mean right-eye astigmatism was 2.05 dioptres, and mean left-eye astigmatism was 2.37 dioptres. The prevalence of astigmatism is greater, in the entire sample, for subjects from age groups 2 and 3 (p<0.005). It shows a tendency to increase with age for patients of group A and in age group 3 (p=0.009). CONCLUSIONS: Astigmatism is more common in patients with ICN than in the general population (65.37 % vs 11.47 %) (p<0.001). Astigmatism increases with age, with a very high statistical significance in patients 13 years old and above (age group 3) when nystagmus is also present. Thus, nystagmus appears to be a predisposing factor for both the presence of astigmatism and the development with the age of high values of this refractive error. This findings should be taken into due account when considering visual dysfunctions in nystagmic patients.

Subtenon injection of natural leukocyte interferon α-2a in diabetic macular edema: a case report.

BACKGROUND: To report the effect of subtenon injections of natural leukocyte interferon α-2a (IFNα) on best corrected visual acuity (BCVA) and central macular thickness (CMT) in a patient with diabetic macular edema (DME). CASE PRESENTATION: A 66-year-old man affected by DME, with glycated hemoglobin (HbA1c) at 6.9%, refractory to laser grid treatment and intravitreal injections of triamcinolone, was selected to receive a cycle of three subtenon injections/week of IFNα (1×106 IU/ml). BCVA and CMT, using spectral domain ocular coherence tomography (SD-OCT), were evaluated preoperatively and at 1 week, 1 month, 4 months, and 1 year postoperatively. BCVA and CMT were significantly improved at 1 week after the three injections (20/200 vs. 20/40 and 498 µm vs. 237 µm, respectively). BCVA remained stable during the 1-year follow-up. CMT was slightly increased, but was still lower than the baseline value (215 µm, 255 µm, and 299 µm during the follow-up visits). No adverse events were recorded, with the exception of mild subconjunctival hemorrhage at the injection site. CONCLUSIONS: IFNα, with its immunomodulatory, anti-proliferative and anti-angiogenic actions, was effective in improving BCVA and reducing CMT in refractory DME. Further randomized controlled studies are required to assess the effect of IFNα alone or in combination with other therapies for DME treatment.

A rapid standardized quantitative microfluidic system approach for evaluating human tear proteins.

PURPOSE: To explore the potential of a chip-based miniaturized capillary gel electrophoresis device in a quantitative evaluation of the human tear protein profile and to validate the method. METHODS: A total of 5 µl of tears were collected from 25 patients diagnosed as having mild to moderate dry eye according to Dry Eye Workshop guidelines and from 20 matched normal volunteers. Protein analysis was performed with the 2100 Bioanalyzer; different protein kit assays were evaluated (Protein 80 kit, Protein 230 kit, High Sensitivity Protein 250 kit) for sizing and quantifying protein samples from 5 to 80 kDa, 14 to 230 kDa, and 5 to 250 kDa, respectively. A standard protein ladder was loaded on each chip to allow an estimation of the appropriate molecular weight of the separated proteins; a sample buffer containing a lower and an upper marker was used to check the correct alignment of each lane. Virtual bands generated by the Bioanalyzer were identified and validated as follows: tear samples were run in parallel and proteins separated by one-dimensional and two-dimensional sodium dodecyl sulfate-PAGE and characterized by immunoblotting, enzymatic digestion, and analysis with liquid chromatography-mass spectrometry followed by a search of the SProt human protein database. RESULTS: Analyses were successfully performed by using as small as a 2 µl tear sample. The Protein 230 kit was selected as the best chip kit, able to differentiate all the proteins of interest. The measurement noise parameters were low, and reproducibility and repeatability exhibited high accuracy (0.998 and 0.995, respectively) and precision (0.974 and 0.977, respectively). The coefficient of variability was slightly higher than that declared by the manufacturer (6.2% versus 5.0%). Total protein content and the following proteins were recognized in all samples: lipophilin A lysozyme C, tear lipocalin-1, zinc-alpha-2-glycoprotein, serotransferrin, lactotransferrin, and exudated serum albumin. CONCLUSIONS: Our data demonstrate that this chip-based tear protein analysis is a reliable method of instrumental diagnosis in daily clinical activity and may provide supporting evaluation parameters for diagnosing and managing tear-based disorders.

Frequency doubling technology, optical coherence technology and pattern electroretinogram in ocular hypertension.

BACKGROUND: To assess which of three methods, namely, optical coherence tomography (OCT), pattern electroretinogram (PERG) or frequency-doubling technology (FDT), is the most sensitive and specific for detecting early glaucomatous damage in ocular hypertension (OH). METHODS: Fifty-two patients with OH (24 men and 28 women, mean age of 56 ± 9.6 years) with an intraocular pressure (IOP) > 21 mm Hg and fifty-two control patients (25 men and 27 women, mean age of 54.8 ± 10.4 years) with IOP < 21 mm Hg, were assessed. All the patients had normal visual acuity, normal optic disk and normal perimetric indices.All subjects underwent OCT, FDT and PERG. Data were analyzed with unpaired t-tests, Chi-square test and Receiver Operating Characteristic (ROC) curve analyses. RESULTS: In patients with OH, OCT showed retinal nerve fiber layer (RNFL) thinner than in control group in the superior quadrant (130.16 ± 10.02 vs 135.18 ± 9.27 µm, respectively; p < 0.011) and inferior quadrant (120.14 ± 11.0 vs 132.68 ± 8.03 µm; p < 0.001). FDT showed a significantly higher pattern standard deviation (PSD) (3.46 ± 1.48 vs 1.89 ± 0.7 dB; p < 0.001). With respect to PERG, only the amplitude showed significant differences (p < 0.044) between the two groups. ROC curve analysis revealed a sensitivity and specificity of 92% and 86%, respectively, for FDT-PSD (with an area under the ROC curve of 0.940), whereas with OCT, a sensitivity of 82% and a specificity of 74% was recorded in the inferior RNFL quadrant (with an area under the ROC curve of 0.806) finally with PERG amplitude we found a sensitivity of 52% and specificity of 77% (with an area under the ROC curve of 0.595). CONCLUSIONS: FDT is the most sensitive and specific method for detecting early glaucomatous damage in eyes with OH, and together with OCT, can be useful in identifying those patients who may develop glaucoma. TRIAL REGISTRATION: ISRCT number: ISRCTN70295497.

Multifocal electroretinogram and Optical Coherence tomography spectral-domain in arc welding macular injury: a case report.

BACKGROUND: the purpose of this study was to report a binocular photic retinal injury induced by plasma arc welding and the follow-up after treatment with vitamin supplements for a month. In our study, we used different diagnostic tools such as fluorescein angiography (FA), optical coherence tomography (OCT) and multifocal electroretinogram (mfERG). CASE PRESENTATION: in the first visit after five days from arc welding injury in the left eye (LE) the visual acuity was 0.9 and 1.0 in the right eye (RE). FA was normal in both eyes. OCT in the left eye showed normal profile and normal reflectivity and one month later, a hyperreflectivity appeared in the external limiting membrane (ELM). The mfERG signal in the LE was 102.30 nV/deg2 five days after the injury and 112.62 nV/deg2 after one month and in the RE respectively 142.70 nV/deg2 and 159.46 nV/deg2. CONCLUSIONS: in cases of retinal photo injury it is important for the ophthalmologist to evaluate tests such as OCT and the mfERG in the diagnosis and follow-up of the patient because the recovery of visual acuity cannot exclude the persistence of phototoxic damage charged to the complex inner-outer segment of photoreceptors.

Crossing the Death Valley of publication process in cornea and ocular surface diseases: from abstracts presented at the Association for Research in Vision and Ophthalmology annual meeting to full-text manuscripts.

PURPOSE: This study was conducted to analyze the profile and publication rate of abstracts in indexed journals presented in the cornea section at the Association for Research in Vision and Ophthalmology Annual Meeting and to further identify potential predictive factors for better outcomes. METHODS: Abstracts accepted for presentation at the 2013 Association for Research in Vision and Ophthalmology Annual Meeting in the cornea section were sought via PubMed and Scopus to identify whether they had been published as full-text manuscripts. First author's name, time of publication, journal's name, and impact factor were recorded. A multivariate regression was performed to explore the association between variables and both the likelihood of publication and the journal's impact factor. A Kaplan-Meier analysis was performed to evaluate the time course of publication of abstracts. RESULTS: Of the 939 analyzed abstracts, 360 (38.3%) were published in journals with a median impact factor of 3.4. The median time interval between abstract submission and article publication was 22 months. The multivariate analysis revealed that abstracts were more likely to be published if they were funded (OR=1.482, p=0.005), had a control group (OR=1.511, p=0.016), and had a basic science research scope (OR=1.388, p=0.020). The journal's impact factor was higher in funded studies (ß=0.163, p=0.002) but lower in multicenter studies (ß=-0.170, p=0.001). The Kaplan-Meier analyses revealed significant differences in the publication time distribution for basic science vs clinical abstracts (χ2=7.636), controlled vs uncontrolled studies (χ2=6.921), and funded vs unfunded research (χ2=13.892) (p<0.05). CONCLUSION: Almost 40% of Association for Research in Vision and Ophthalmology abstracts were published within 5 years from submission. Funding support, basic research scope, and controlled design were the determinants of better outcomes of publication.

ET-1 plasma levels and ocular blood flow in retinitis pigmentosa.

Retinitis pigmentosa (RP) is an inherited retinal disorder clinically characterized by a pale, waxy optic nerve head, attenuated retinal blood vessels, and bone spicule pigment in the retina. Hemodynamic studies have demonstrated that RP is associated with a reduction in the retinal and choroidal blood flow. Retinal hemodynamic impairment is also present in early stages of RP, and various hypotheses have been advanced as to the cause. The authors studied 20 patients, 12 males and 8 females, aged 26-42 years (mean 35.1 years) and affected by simplex RP. The patients had a visual acuity of 0.9 +/- 0.1, visual field mean defect of -6.52 +/- 3.58 dB, and b-wave electroretinogram amplitude of 260.08 +/- 8.24 microV. An increase in plasma levels of endothelin-1 (ET-1) was found: 1.910 +/- 0.317 pg/mL versus 1.180 +/- 0.210 pg/mL in non-RP controls (p < 0.02). Moreover both an ocular and systemic vascular impairment was detected by means of color Doppler imaging and laser Doppler flowmetry performed during a cold pressor test. We found a correlation between the increase of ET-1 plasma levels in RP and the decrease of peak systolic velocity in the ophthalmic artery (p < 0.03) and in the posterior ciliary arteries (p < 0.006). It is thought that an increase of ET-1 and retinal oxygen levels in RP could lead to vasoconstriction and a decrease of the retinal blood flow, worsening the abiotrophic process.

Do bifocals reduce accommodative amplitude in convergence excess esotropia?

BACKGROUND: As therapy with bifocal lenses can generate a condition of acquired hypo-accommodation, we assessed the results of bifocal therapy in children with non-refractive accommodative esotropia in whom near point of accommodation (NPA) was measured before the prescription of the lenses and at the end of the study. METHODS: We examined 28 consecutive patients orthophoric for far, but with esotropia due to excess convergence for near (group 1), and 28 matched controls, orthophoric for far and near (group 2). The patients were prescribed bifocal lenses between the age of 5 and 8. The NPA was measured at time zero and after 4 years of follow-up in both groups. RESULTS: NPA values, measured at time 0, were lower than average (10 dioptres) in ten of the 28 patients in group 1, and increased over the 4 years of follow-up without exceeding 10 dioptres. Only one of the other 18 patients in group 1, with normal NPA, had a lower value at the end of the study, although the values were still above 10 dioptres. CONCLUSIONS: In several patients, excessive convergence is secondary to the extra accommodative effort required due to the presence of a primitive NPA deficit. In these subjects, the prognosis can be made on the basis of NPA measurement, and treatment with bifocal lenses will always be required to compensate. Furthermore, the parents of these small patients should be informed, even before the prescription of bifocals, that prospective surgery of medial rectus muscles will not eliminate the need for bifocals.

In Vivo and Ex Vivo Comprehensive Evaluation of Corneal Reinnervation in Eyes Neurotized With Contralateral Supratrochlear and Supraorbital Nerves.

PURPOSE: To use an automated morphometric analysis system of in vivo confocal microscopy (IVCM) images for evaluating reinnervation occurring at the subbasal nerve plexus (SNP) after direct corneal neurotization (DCN) and to further report neurophysiological and histopathological findings. METHODS: Prospective interventional case series including 3 eyes with neurotrophic keratitis that underwent DCN. Deep anterior lamellar keratoplasty was performed 18 months after DCN in patient 1. The following evaluations were performed before and at 3, 6, and 12 months after DCN: clinical evolution of keratitis; corneal sensitivity; IVCM images of the SNP analyzed with "ACCMetrics;" neurophysiological study of corneal reflex. Protein gene product 9.5 immunofluorescence staining assay and transmission electron microscopy were conducted on the neurotized button excised during deep anterior lamellar keratoplasty. RESULTS: Complete healing was obtained in all patients by 3 months postoperatively. Corneal sensitivity was absent preoperatively in all eyes and improved after surgery, reaching an average value of 30 mm 1 year postoperatively. The corneal SNP was not visible at IVCM in any of the cases preoperatively and became visible by 3 months postoperatively, showing IVCM metrics comparable to normal contralateral eyes at 1 year. In all cases, neurophysiological evaluation showed a partial recovery of the electrical activity of the cornea. In patient 1, protein gene product (PGP) 9.5 staining of neurotized cornea showed nerve fascicles at the SNP, whereas transmission electron microscopy showed amyelinic nerve axons and nerve endings. CONCLUSIONS: The corneal SNP exhibited IVCM metrics comparable to the normal contralateral eye 1 year after DCN. Ex vivo histopathological assessment of neurotized corneas confirmed the presence of nerves with normal ultrastructure.

Direct Versus Indirect Corneal Neurotization for the Treatment of Neurotrophic Keratopathy: A Multicenter Prospective Comparative Study.

PURPOSE: To analyze the comparative safety and efficacy of two techniques of corneal neurotization (CN) (direct corneal neurotization [DCN] vs indirect corneal neurotization [ICN]) for the treatment of neurotrophic keratopathy (NK). DESIGN: Multicenter interventional prospective comparative case series. METHODS: This study took place at ASST Santi Paolo e Carlo University Hospital, Milan; S.Orsola-Malpighi University Hospital, Bologna; and Santa Maria alle Scotte University Hospital, Siena, Italy. The study population consisted of consecutive patients with NK who underwent CN between November 2014 and October 2019. The intervention procedures included DCN, which was was performed by transferring contralateral supraorbital and supratrochlear nerves. ICN was performed using a sural nerve graft. The main outcome measures included NK healing, corneal sensitivity, corneal nerve fiber length (CNFL) measured by in vivo confocal microscopy (IVCM), and complication rates. RESULTS: A total of 26 eyes in 25 patients were included: 16 eyes were treated with DCN and 10 with ICN. After surgery, NK was healed in all patients after a mean period of 3.9 months without differences between DCN and ICN. Mean corneal sensitivity improved significantly 1 year after surgery (from 3.07 to 22.11 mm; P < .001) without differences between the 2 groups. The corneal sub-basal nerve plexus that was absent before surgery in all patients, except 4, become detectable in all cases (mean CNFL: 14.67 ± 7.92 mm/mm2 1 year postoperatively). No major complications were recorded in both groups. CONCLUSIONS: CN allowed the healing of NK in all patients as well as improvement of corneal sensitivity in most of them thanks to nerve regeneration documented by IVCM. One year postoperatively, DCN and ICN showed comparable outcomes.

Intraocular inflammation after Ultrasound Cyclo Plasty for the treatment of glaucoma.

This is a prospective interventional clinical study evaluating intraocular inflammation developed after Ultrasound Cyclo Plasty (UCP) for the treatment of glaucoma. Eighteen eyes of 18 patients were treated with UCP second-generation probes (Eye OP1). After treatment, the mean intraocular pressure (IOP) significantly decreased from 26.8±7.2 to 18.8±6.1 mm Hg at day 1 and to 14.7±3.4 mm Hg at month 6 (all P<0.001). Mean laser flare-cell photometry value steeply increased after surgery from 12.1±7.5 to 64.1±53.9 ph/ms (P=0.001) at day 1, and then progressively decreased to respectively 60.6±49.7 at day 7, 43.5±38.5 at day 14 and 28.2±18.3 at month 1 (all P<0.05), returning at levels similar to baseline ones at month 3 and month 6 (respectively 16.7±6.2 and 12.8±10.2, both P>0.05). A significant negative correlation was found between postoperative increase of aqueous flare values and anterior chamber depth (R=-0.568, P=0.014). This timeframe may be considered reasonable for repeating UCP treatment, when required.

Choroidal Vascular Changes in Arteritic and Nonarteritic Anterior Ischemic Optic Neuropathy.

PURPOSE: To compare choroidal vascularity index (CVI) in patients with arteritic anterior ischemic optic neuropathy (A-AION), nonarteritic anterior ischemic optic neuropathy (NA-AION), and control subjects. DESIGN: Retrospective cross-sectional study. METHODS: This study was conducted at the Ophthalmology Unit of the S.Orsola-Malpighi University Hospital (Bologna, Italy). Macular and optic nerve head optical coherence tomography (OCT) scans of 20 patients with A-AION secondary to giant cell arteritis (biopsy-proven), 20 patients with NA-AION, and 20 control subjects were acquired with Heidelberg Spectralis (Heidelberg Engineering, Heidelberg, Germany). Images were binarized using ImageJ software, and total choroid area (TCA), luminal area (LA), and stromal area (SA) were segmented. The main outcome measure was CVI, defined as the ratio of LA to TCA. RESULTS: Patients with A-AION showed a significantly lower macular and peripapillary CVI compared to both patients with NA-AION (respectively, 67.17 ± 2.35 vs 69.66 ± 4.18, P = .048; 63.51 ± 3.29 vs 67.67 ± 3.07, P < .001) and control subjects (respectively, 67.17 ± 2.35 vs 70.00 ± 2.95, P = .021; 63.51 ± 3.29 vs 68.69 ± 3.19, P = .002). Conversely, no significant difference in macular and peripapillary CVI was found between patients with NA-AION and controls (respectively, P = .942 and P = .570). After adjustment for age, the difference of peripapillary CVI among groups remained statistically significant (P < .001), while the difference in macular CVI did not (P = .060). CONCLUSIONS: Macular and peripapillary CVI are reduced in patients with A-AION. These parameters may be useful to quantitatively evaluate choroidal vascular dysfunction in A-AION, serving as a new additional diagnostic tool to distinguish A-AION from NA-AION.