Gene Therapy in Hereditary Retinal Dystrophies: The Usefulness of Diagnostic Tools in Candidate Patient Selections.

PURPOSE: Gene therapy actually seems to have promising results in the treatment of Leber Congenital Amaurosis and some different inherited retinal diseases (IRDs); the primary goal of this strategy is to change gene defects with a wild-type gene without defects in a DNA sequence to achieve partial recovery of the photoreceptor function and, consequently, partially restore lost retinal functions. This approach led to the introduction of a new drug (voretigene neparvovec-rzyl) for replacement of the RPE65 gene in patients affected by Leber Congenital Amaurosis (LCA); however, the treatment results are inconstant and with variable long-lasting effects due to a lack of correctly evaluating the anatomical and functional conditions of residual photoreceptors. These variabilities may also be related to host immunoreactive reactions towards the Adenovirus-associated vector. A broad spectrum of retinal dystrophies frequently generates doubt as to whether the disease or the patient is a good candidate for a successful gene treatment, because, very often, different diseases share similar genetic characteristics, causing an inconstant genotype/phenotype correlation between clinical characteristics also within the same family. For example, mutations on the RPE65 gene cause Leber Congenital Amaurosis (LCA) but also some forms of Retinitis Pigmentosa (RP), Bardet Biedl Syndrome (BBS), Congenital Stationary Night Blindness (CSNB) and Usher syndrome (USH), with a very wide spectrum of clinical manifestations. These confusing elements are due to the different pathways in which the product protein (retinoid isomer-hydrolase) is involved and, consequently, the overlapping metabolism in retinal function. Considering this point and the cost of the drug (over USD one hundred thousand), it would be mandatory to follow guidelines or algorithms to assess the best-fitting disease and candidate patients to maximize the output. Unfortunately, at the moment, there are no suggestions regarding who to treat with gene therapy. Moreover, gene therapy might be helpful in other forms of inherited retinal dystrophies, with more frequent incidence of the disease and better functional conditions (actually, gene therapy is proposed only for patients with poor vision, considering possible side effects due to the treatment procedures), in which this approach leads to better function and, hopefully, visual restoration. But, in this view, who might be a disease candidate or patient to undergo gene therapy, in relationship to the onset of clinical trials for several different forms of IRD? Further, what is the gold standard for tests able to correctly select the patient? Our work aims to evaluate clinical considerations on instrumental morphofunctional tests to assess candidate subjects for treatment and correlate them with clinical and genetic defect analysis that, often, is not correspondent. We try to define which parameters are an essential and indispensable part of the clinical rationale to select patients with IRDs for gene therapy. This review will describe a series of models used to characterize retinal morphology and function from tests, such as optical coherence tomography (OCT) and electrophysiological evaluation (ERG), and its evaluation as a primary outcome in clinical trials. A secondary aim is to propose an ancillary clinical classification of IRDs and their accessibility based on gene therapy's current state of the art. MATERIAL AND METHODS: OCT, ERG, and visual field examinations were performed in different forms of IRDs, classified based on clinical and retinal conditions; compared to the gene defect classification, we utilized a diagnostic algorithm for the clinical classification based on morphofunctional information of the retina of patients, which could significantly improve diagnostic accuracy and, consequently, help the ophthalmologist to make a correct diagnosis to achieve optimal clinical results. These considerations are very helpful in selecting IRD patients who might respond to gene therapy with possible therapeutic success and filter out those in which treatment has a lower chance or no chance of positive results due to bad retinal conditions, avoiding time-consuming patient management with unsatisfactory results.

Identifying Meibomian Gland Dysfunction Biomarkers in a Cohort of Patients Affected by DM Type II.

(1) Background: Meibomian gland dysfunction (MGD) among patients with diabetes mellitus (DM) is a common manifestation of dry eye syndrome (DES). (2) Methods: The purpose of this study is to identify clinical parameters and biomarkers useful to improve the follow-up and the treatment of these patients. We have used an ocular surface disease index (OSDI) questionnaire, Schirmer test I/II, tear film break-up time (TF-BUT), fluorescein plus lissamine green staining, Marx's line (ML), and meibomian gland (MGs) morphology using Sirius® Topographer (CSO, Costruzione Strumenti Oftalmici, Florence, Italy). Blood sample analysis included glucose, glycated hemoglobin, lipid profile, cortisol, dehydroepiandrosterone sulfate (DHEA-S), androstenedione (ASD) and testosterone. (3) Results: Cortisol and ASD were positively correlated with an increase of MG tortuosity, and an Increased level of triglycerides was associated with a reduction of MGs length. DHEAS levels lowered with age and were associated with ocular surface staining. (4) Conclusions: Future studies, perhaps including meibum lipid analysis and tear cytokine levels, may also further elucidate the connection between these parameters, MG architecture and function.

Corneal nerve regeneration is affected by scar location in herpes simplex keratitis: A longitudinal in vivo confocal microscopy study.

PURPOSE: To assess the effect of corneal scar location on corneal nerve regeneration in patients with herpes simplex virus (HSV) keratitis in their affected and contralateral eyes over a 1-year period by in vivo confocal microscopy (IVCM), and to correlate these findings to corneal sensation measured by Cochet-Bonnet Esthesiometer. METHODS: Prospective, longitudinal, case-control study. Bilateral corneal nerve density and corneal sensation were analyzed centrally and peripherally in 24 healthy controls and 23 patients with unilateral HSV-related corneal scars using IVCM. RESULTS: In the central scar (CS) group, total nerve density in the central cornea remained significantly lower compared to controls at follow-up (11.05 ± 1.97mm/mm2, p < 0.001), and no significant nerve regeneration was observed (p = 0.090). At follow-up, total nerve density was not significantly different from controls in the central and peripheral cornea of the peripheral scar (PS) group (all p > 0.05), but significant nerve regeneration was observed in central corneas (16.39 ± 2.39mm/mm2, p = 0.007) compared to baseline. In contralateral eyes, no significant corneal nerve regeneration was observed in central or peripheral corneas of patients with central scars or peripheral scars at 1-year follow-up, compared to baseline (p > 0.05). There was a positive correlation between corneal nerve density and sensation in both central (R = 0.53, p < 0.0001) and peripheral corneas (R = 0.27, p = 0.0004). In the CS group, the corneal sensitivity was <4 cm in 4 (30.8%) and 7 (53.8%) patients in the central and peripheral corneas at baseline, and in 5 (38.5%) and 2 subjects (15.4%) at follow-up, whereas in the PS group only 1 patient (10%) showed a corneal sensation < 4 cm in the central cornea at baseline, and only 1 (10.0%), 3 (30.0%) and 1 (10.0%) patients at follow-up in the central, affected and opposite area of the cornea, respectively. CONCLUSION: The location of HSV scarring in the cornea affects the level of corneal nerve regeneration. Eyes with central corneal scar have a diminished capacity to regenerate nerves in central cornea, show a more severe reduction in corneal sensation in the central and peripheral corneas that persist at follow-up, and have a reduced capability to restore the corneal sensitivity above the cut-off of 4 cm. Thus, clinicians should be aware that CS patients would benefit from closer monitoring for potential complications associated with neurotrophic keratopathy, as they have a lower likelihood for nerve regeneration.

Persistence of Juvenile Idiopathic Arthritis-Associated Uveitis in Adulthood: A Retrospective Study.

Background: Juvenile idiopathic arthritis (JIA) is a rheumatic condition of childhood that is frequently associated with anterior chronic uveitis. Evidence suggests that uveitis may persist up to adulthood in some cases, possibly causing severe visual impairment. Methods: We conducted a retrospective study on a series of patients aged 16 years or older with JIA-related active uveitis who were referred to the Uveitis Service of Sapienza University of Rome from 1990 to 2019 to evaluate the characteristics of ocular disease in patients with JIA-associated uveitis (JIA-U) who still exhibit uveitis in adulthood. Data on clinical features, treatment, complications and visual outcomes were collected. Results: Twenty adults (85% female; median age 23.4 ± 6.6 years, range 16−38 years) with ongoing uveitis (35 eyes) were identified. The median age at JIA onset was 6.15 ± 2.9 years (range 2−10), and uveitis onset was 8.7 ± 4.7 years (range 3−20). The patients were observed in a median follow-up of 16 ± 7.7 years (range 4−35). Fifty-seven percent of affected eyes (20 eyes) had good visual acuity (>0.4 logMAR), while eleven percent of affected eyes (4 eyes) were blind (≤20/200). Uveitis required topical steroids and mydriatic/cycloplegic in all cases. Orbital steroid injection was performed in 13 eyes. Systemic corticosteroids and biologic drugs were used in 14 patients. Conclusions: Although the visual prognosis of JIA-U has improved in recent years, persistent uveitis up to adulthood is still observed. Therefore, protracted follow-up of JIA-U patients is warranted because of the high burden of delayed visual complications.

REP1 deficiency causes systemic dysfunction of lipid metabolism and oxidative stress in choroideremia.

Choroideremia (CHM) is an X-linked recessive chorioretinal dystrophy caused by mutations in CHM, encoding for Rab escort protein 1 (REP1). Loss of functional REP1 leads to the accumulation of unprenylated Rab proteins and defective intracellular protein trafficking, the putative cause for photoreceptor, retinal pigment epithelium (RPE), and choroidal degeneration. CHM is ubiquitously expressed, but adequate prenylation is considered to be achieved, outside the retina, through the isoform REP2. Recently, the possibility of systemic features in CHM has been debated; therefore, in this study, whole metabolomic analysis of plasma samples from 25 CHM patients versus age- and sex-matched controls was performed. Results showed plasma alterations in oxidative stress-related metabolites, coupled with alterations in tryptophan metabolism, leading to significantly raised serotonin levels. Lipid metabolism was disrupted with decreased branched fatty acids and acylcarnitines, suggestive of dysfunctional lipid oxidation, as well as imbalances of several sphingolipids and glycerophospholipids. Targeted lipidomics of the chmru848 zebrafish provided further evidence for dysfunction, with the use of fenofibrate over simvastatin circumventing the prenylation pathway to improve the lipid profile and increase survival. This study provides strong evidence for systemic manifestations of CHM and proposes potentially novel pathomechanisms and targets for therapeutic consideration.

Update on Gene Therapy Clinical Trials for Choroideremia and Potential Experimental Therapies.

Background and objectives: Choroideremia (CHM) is an X-linked recessive chorioretinal dystrophy caused by mutations involving the CHM gene. Gene therapy has entered late-phase clinical trials, although there have been variable results. This review gives a summary on the outcomes of phase I/II CHM gene therapy trials and describes other potential experimental therapies. Materials and Methods: A Medline (National Library of Medicine, Bethesda, MD, USA) search was performed to identify all articles describing gene therapy treatments available for CHM. Results: Five phase I/II clinical trials that reported subretinal injection of adeno-associated virus Rab escort protein 1 (AAV2.REP1) vector in CHM patients were included. The Oxford study (NCT01461213) included 14 patients; a median gain of 5.5 ± 6.8 SD (-6 min, 18 max) early treatment diabetic retinopathy study (ETDRS) letters was reported. The Tubingen study (NCT02671539) included six patients; only one patient had an improvement of 17 ETDRS letters. The Alberta study (NCT02077361) enrolled six patients, and it reported a minimal vision change, except for one patient who gained 15 ETDRS letters. Six patients were enrolled in the Miami trial (NCT02553135), which reported a median gain of 2 ± 4 SD (-1 min, 10 max) ETDRS letters. The Philadelphia study (NCT02341807) included 10 patients; best corrected visual acuity (BCVA) returned to baseline in all by one-year follow-up, but one patient had -17 ETDRS letters from baseline. Overall, 40 patients were enrolled in trials, and 34 had 2 years of follow-up, with a median gain of 1.5 ± 7.2 SD (-14 min, 18 max) in ETDRS letters. Conclusions: The primary endpoint, BCVA following gene therapy in CHM, showed a marginal improvement with variability between trials. Optimizing surgical technique and pre-, peri-, and post-operative management with immunosuppressants to minimize any adverse ocular inflammatory events could lead to reduced incidence of complications. The ideal therapeutic window needs to be addressed to ensure that the necessary cell types are adequately transduced, minimizing viral toxicity, to prolong long-term transgenic potential. Long-term efficacy will be addressed by ongoing studies.

Prospective deep phenotyping of choroideremia patients using multimodal structure-function approaches.

OBJECTIVE: To investigate the retinal changes in choroideremia (CHM) patients to determine correlations between age, structure and function. SUBJECTS/METHODS: Twenty-six eyes from 13 male CHM patients were included in this prospective longitudinal study. Participants were divided into <50-year (n = 8) and ≥50-year (n = 5) old groups. Patients were seen at baseline, 6-month, and 1-year visits. Optical coherence tomography (OCT), OCT angiography, and fundus autofluorescence were performed to measure central foveal (CFT) and subfoveal choroidal thickness (SCT), as well as areas of preserved choriocapillaris (CC), ellipsoid zone (EZ), and autofluorescence (PAF). Patients also underwent functional investigations including visual acuity (VA), contrast sensitivity (CS), colour testing, microperimetry, dark adaptometry, and handheld electroretinogram (ERG). Vision-related quality-of-life was assessed by using the NEI-VFQ-25 questionnaire. RESULTS: Over the 1-year follow-up period, progressive loss was detected in SCT, EZ, CC, PAF, and CFT. Those ≥50-years exhibited more structural and functional defects with SCT, EZ, CC, and PAF showing strong correlation with patient age (rho ≤ -0.47, p ≤ 0.02). CS and VA did not change over the year, but CS was significantly correlated with age (rho = -0.63, p = 0.001). Delayed to unmeasurable dark adaptation, decreased colour discrimination and no detectable ERG activity were observed in all patients. Minimal functional deterioration was observed over one year with a general trend of slower progression in the ≥50-years group. CONCLUSIONS: Quantitative structural parameters including SCT, CC, EZ, and PAF are most useful for disease monitoring in CHM. Extended follow-up studies are required to determine longitudinal functional changes.

Visualization of microneuromas by using in vivo confocal microscopy: An objective biomarker for the diagnosis of neuropathic corneal pain?

PURPOSE: The diagnosis of neuropathic corneal pain (NCP) is challenging, as it is often difficult to differentiate it from conventional dry eye disease (DED). In addition to eye pain, NCP can present with similar signs and symptoms of DED. The purpose of this study is to find an objective diagnostic sign to identify patients with NCP, using in vivo confocal microscopy (IVCM). METHODS: This was a comparative, retrospective, case-control study. Patients with clinical diagnosis of NCP (n = 25), DED (n = 30), and age- and sex-matched healthy controls (n = 16), who underwent corneal imaging with IVCM (HRT3/RCM) were included. Central corneal IVCM scans were analyzed by 2 masked observers for nerve density and number, presence of microneuromas (terminal enlargements of subbasal corneal nerve) and/or nerve beading (bead-like formation along the nerves), and dendritiform cell (DC) density. RESULTS: There was a decrease in total nerve density in both NCP (14.14 ± 1.03 mm/mm2) and DED patients (12.86 ± 1.04 mm/mm2), as compared to normal controls (23.90 ± 0.92 mm/mm2; p < 0.001). However, total nerve density was not statistically different between NCP and DED patients (p = 0.63). Presence of nerve beading was not significantly different between patients and normal controls (p = 0.15). Interestingly, microneuromas were observed in all patients with NCP, while they were not present in any of the patients with conventional DED (sensitivity and specificity of 100%). DC density was significantly increased in both NCP (71.89 ± 16.91 cells/mm2) and DED patients (111.5 ± 23.86 cells/mm2), as compared to normal controls (24.81 ± 4.48 cells/mm2 (p < 0.05). However, there was no significant difference in DC density between DED and NCP patients (p = 0.31). CONCLUSION: IVCM may be used as an adjunct diagnostic tool for the diagnosis of NCP in the presence of neuropathic symptoms. Microneuromas may serve as a sensitive and specific biomarker for the diagnosis of NCP.

An Unusual Retinal Vessel Modification in Patients Affected by JIA-Uveitis with a Follow-Up Longer Than 16 Years.

PURPOSE: To report unusual and rare clinical changes of retinal vessel pattern in a series of patients affected by Juvenile Idiopathic Arthritis (JIA) uveitis with a follow-up longer than 16 years. METHODS: A series of three patients with JIA-uveitis followed at the University of Rome "Sapienza" from 1998 to 2014 were reported. The retinal vessels were analyzed with fluorescein angiography using Heidelberg Retinal Angiogram-2 (HRA-2; Heidelberg Engineering GmBH, Dossenheim, Germany) and the Topcon TRC-50LX retinal camera (Topcon Europe, The Netherlands). A Spectralis Domain OCT (SD-OCT) (Spectralis Family Heidelberg, Germany) was performed to evaluate vessel anatomy. RESULTS: Fundus photography showed sheathed vessels localized around the optic disc in every case. Angiography revealed a normal physiology of vessel walls and flow; no sheathing or leakage of dye was observed. SD-OCT demonstrated reflective vessel walls. Vessel lumen appeared patent, and the normal "hourglass configuration" was blurred, but identifiable. CONCLUSIONS: Vessel modifications observed in long-standing JIA-uveitis are not signs of vascular inflammation and are not associated to hypoperfusion. In these cases, ophthalmologists should avoid further invasive investigation and should consider introducing SD-OCT as a routine method to evaluate the vessel changes during the follow-up.

In Vivo Confocal Microscopy Demonstrates Increased Immune Cell Densities in Corneal Graft Rejection Correlating With Signs and Symptoms.

PURPOSE: Diagnosis of graft rejection is based on patient symptoms and on clinical signs detected by slit-lamp biomicroscopy. This study investigated whether laser in vivo confocal microscopy (IVCM) can aid in the diagnosis of corneal graft rejection by detecting cellular corneal changes that take place after transplantation. DESIGN: Prospective case-control study. SUBJECTS: Thirty-eight eyes of 38 patients with penetrating keratoplasty (15 eyes with corneal graft rejection, 23 eyes without rejection) and 9 age-matched normal controls. METHODS: Laser IVCM was performed in the corneal grafts centrally. The density of immune cells (IC) was assessed for epithelial, sub-epithelial, stromal, and endothelial layers by 2 masked observers. IC density was compared among different groups and correlated to clinical signs and symptoms of corneal graft rejection. MAIN OUTCOME MEASUREMENTS: Outcome measurement was the IC density in the corneal layers and its associations with the presence of clinical signs and symptoms of corneal graft rejection. RESULTS: The IC density was significantly different between rejected and non-rejected grafts (P = 0.004) and different from that of normal controls (P = 0.001). Among corneal layers, IC density was significantly higher in rejected grafts than in non-rejected grafts in only the sub-basal (611.54 ± 573.74 vs. 340.61 ± 268.60 cells/mm2, respectively; P = 0.049) and endothelial layers (250.62 ± 267.13 vs. 103.47 ± 81.91 cells/mm2, respectively; P = 0.001). Patients with decreased best corrected visual acuity, Khodadoust line, and anterior chamber cells demonstrated a significant increase in total IC density (P < 0.05), whereas patients with symptoms of irritation, light sensitivity, and pain revealed a specific increase in IC density in the sub-basal layer (P < 0.05). Patients with ocular pain had higher IC density in the epithelial layer than those without pain (P = 0.03). CONCLUSIONS: Patients with corneal graft rejection demonstrate a significant increase in corneal immune cells, particularly, in the sub-basal and endothelial layers compared to patients with non-rejected grafts and controls. Although symptoms associated with endothelial rejection demonstrate a general increase in IC, pain, irritation, and light sensitivity are associated with increased IC in the sub-basal layer. Assessment of patients with corneal graft rejection by IVCM may serve as an adjunctive tool in the diagnosis and management of corneal graft rejection.

Active surveillance of choroidal neovascularisation in children: incidence, aetiology and management findings from a national study in the UK.

BACKGROUND/AIMS: To determine the UK incidence, demographics, aetiology, management and visual outcome for children developing choroidal neovascularisation (CNV). METHODS: A prospective population-based observational study of routine practice via the British Ophthalmological Surveillance Unit between January 2012 and December 2013 with subsequent 1-year follow-up in children under 16 years old with newly diagnosed CNV. RESULTS: Twenty-seven children with CNV were reported. The UK estimated annual incidence for those aged 16 and under was 0.21 per 100 000 (95% CI 0.133 to 0.299). The mean age was 11.1 years (SD 3.9, range 4-16). Fourteen were female. Seventy-seven per cent (22 patients) were Caucasian British. Twenty-three children (85%) had unilateral disease. The most common aetiology included inflammatory retinochoroidopathy (n=9), optic disc abnormalities (n=9) and idiopathic (n=5). Optical coherence tomography was performed in all cases and fundus fluorescein angiography in 61%. Management included observation only (n=10), anti-vascular endothelial growth factor (anti-VEGF) injection of bevacizumab (n=14) or ranibizumab (n=2), or both (n=1), and additional use of oral (n=1) and local (periocular n=2 and intravitreal n=2) steroids in five children with inflammatory retinochoroidopathy. The mean number of anti-VEGF injections was 2±1, with eight patients receiving only one injection. The mean (SD) best corrected visual acuity in LogMAR was 0.91 (0.53) at presentation and 0.74 (0.53) at 1-year follow-up (p=0.09). CONCLUSION: This is the first population-based prospective study of CNV in children. This is a rare disorder with a poor visual prognosis irrespective of CNV location and the use of anti-VEGF therapy.

Quantitative and Qualitative Features of Spectral-Domain Optical Coherence Tomography Provide Prognostic Indicators for Visual Acuity in Patients With Choroideremia.

BACKGROUND AND OBJECTIVE: To identify qualitative and quantitative features of spectral-domain optical coherence tomography (SD-OCT) as prognostic indicators of visual acuity (VA) loss in patients with choroideremia (CHM). PATIENTS AND METHODS: Retrospective study of 57 male patients with CHM. Central foveal thickness (CFT), subfoveal choroidal thickness (SCT), fundus autofluorescence area, and evidence of outer retinal and choroidal degeneration were analyzed by SD-OCT. RESULTS: Best-corrected VA logMAR at baseline was associated with CFT at baseline (r = -0.47; P < .01), CFT at most recent follow-up (r = -0.27; P < .01), and SCT at baseline (r = -0.31; P < .01). Ellipsoid zone (EZ) rupture was associated with a higher CFT loss (r = 0.33; P < .01) and macular cystic spaces (MCS) with a reduction in VA over time (hazard risk = 0.48; P = .05). CONCLUSION: Reduced CFT at baseline, EZ rupture, and MCS are poor prognostic indicators for VA outcome. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:711-716.].

Variant lattice corneal dystrophy associated with compound heterozygous mutations in the TGFBI gene.

BACKGROUND/AIMS: To report the clinical, histopathological and genetic features of a variant of lattice corneal dystrophy (LCD) associated with two pathogenic mutations in the transforming growth factor-B-induced (TGFBI) gene. METHODS: Clinical characterisation was performed by slit lamp examination and in vivo confocal microscopic imaging (IVCM). Histopathological characterisation was performed with light microscopic examination of an excised corneal button and a peripheral blood samples were collected for TGFBI screening. RESULTS: A 42-year-old woman presented with progressive photophobia and decreased visual acuity in both eyes. Slit lamp examination demonstrated punctate and linear branching opacities in the mid and posterior corneal stroma, corresponding to hyper-reflective opacities noted on IVCM and amyloid deposition noted on histopathological examination of an excised corneal button. TGFBI screening revealed two previously reported heterozygous missense mutations: c.337G>A (p.(Val113Ile)) in exon 4 and c.1673T>C (p.(Leu558Pro)) in exon 12. Screening of an affected sibling with a similar phenotype revealed that she was also heterozygous for both mutations, while screening of another sibling with punctate but not linear stromal opacities revealed that she was heterozygous for only the p.(Leu558Pro) mutation. CONCLUSIONS: The p.(Val113Ile) mutation results in an alteration of the atypical LCD phenotype associated with the p.(Leu558Pro) mutation. This represents only the second report of the alteration of the phenotype of a TGFBI dystrophy by a second, non-homozygous pathogenic mutation, and thus provides insight into the phenotype-genotype correlation of the TGFBI dystrophies.

Psoriasis and Psoriatic Arthritis-Related Uveitis: Different Ophthalmological Manifestations and Ocular Inflammation Features.

PURPOSE: To compare clinical features of uveitis in patients affected by psoriasis and psoriatic arthritis (PsA). METHODS: A retrospective case-control study. RESULTS: 117 patients were affected by uveitis and psoriasis or PsA (92 and 25 patients, respectively) from 2003 to 2013. Axial PsA was associated with unilateral uveitis onset compared to the peripheral pattern (p < 0.03). The prevalence of eyes with at least one complication involving anterior segment was significantly more represented in the PsA group than the psoriasis one (p = 0.024). Anterior segment complications were more frequently associated with posterior ones in PsA patients than in psoriasis patients (p = 0.005). Most common complications in total sample at baseline examination were cataract (29.7%), ocular hypertension (17%), macular edema (7%), and pupillary seclusion (4.4%). CONCLUSION: Uveitis in patients with psoriasis and PsA may have distinguishing clinical features. PsA patients have more ocular complications than those with psoriasis. Both groups need an ophthalmological examination to promptly detect ocular co-morbidity.

Detection of subclinical keratoconus through non-contact tonometry and the use of discriminant biomechanical functions.

The purpose of the present study was to develop a discriminant function departing from the biomechanical parameters provided by a non-contact tonometer (Corvis-ST, Oculus Optikgeräte, Wetzlar, Germany) to distinguish subclinical keratoconus from normal eyes. 212 eyes (120 patients) were divided in two groups: 184 healthy eyes of 92 patients aged 32.99 ± 7.85 (21-73 years) and 28 eyes of 28 patients aged 37.79 ± 14.21 (17-75 years) with subclinical keratoconus. The main outcome measures were age, sex, intraocular pressure (IOP), corneal central thickness (CCT) and other specific biomechanical parameters provided by the tonometer. Correlations between all biomechanical parameters and the rest of variables were evaluated. The biomechanical measures were corrected in IOP and CCT (since these variable are not directly related with the corneal structure and biomechanical behavior) to warrant an accurate comparison between both types of eyes. Two discriminant functions were created from the set of corrected variables. The best discriminant function created depended on three parameters: maximum Deformation Amplitude (corrected in IOP and CCT), First Applanation time (corrected in CCT) and CCT. Statistically significant differences were found between groups for this function (p=2·10(-10); Mann-Withney test). The area under the Receiving Operating Characteristic was 0.893 ± 0.028 (95% confidence interval 0.838-0.949). Sensitivity and specificity were 85.7% and 82.07% respectively. These results show that the use of biomechanical parameters provided by non-contact tonometry, previous normalization, combined with the theory of discriminant functions is a useful tool for the detection of subclinical keratoconus.

Fifteen years follow-up of photorefractive keratectomy up to 10 D of myopia: outcomes and analysis of the refractive regression.

PURPOSE: To evaluate outcomes of photorefractive keratectomy up to -10.00 D of myopia and -4.50 of astigmatism and to develop a predictive model for the refractive changes in the long term. SETTING: Vissum Corporation and Miguel Hernandez University (Alicante, Spain). DESIGN: Retrospective-prospective observational series of cases. METHODS: This study included 33 eyes of 33 patients aged 46.79±7.04 years (range 40-57) operated with the VISX 20/20 excimer laser with optical zones of 6 mm. No mitomycin C was used in any of these cases. The minimum follow-up was 15 years. The main outcome measures were: uncorrected and corrected distance visual acuity, manifest refraction and corneal topography. Linear regression models were developed from the observed refractive changes over time. RESULTS: Safety and efficacy indexes at 15 years were 1.18 and 0.83, respectively. No statistically significant differences were detected for any keratometric variable during the follow-up (p≥0.103). 15 years after the surgery 54.55% of the eyes were within ±1.00 D of spherical equivalent and 84.85% within ±2.00 D. The uncorrected distance visual acuity at 15 years was 20/25 or better in 60.6% of the eyes and 20/40 or better in 72.73% of the eyes. The correlation between the attempted and the achieved refractions was r=0.948 (p<0.001) at 1 year, and r=0.821 (p<0.001) at 15 years. No corneal ectasia was detected in any case during the follow-up. CONCLUSIONS: Photorefractive keratectomy is a safe refractive procedure in the long term within the range of myopia currently considered suitable for its use, although its efficacy decreases with time, especially, in high myopia. The model developed predicts a myopic regression of 2.00 D at 15 years for an ablation depth of 130 µm.

Contact Lens Care among Teenage Students in Italy: A Cross-Sectional Study.

AIM: To assess the attitude and practice of contact lens (CL) wearers among teenage school students and to evaluate how much the teenagers adhere to the CL care procedures according to the proper care of CL guidelines. METHODS: A cross-sectional descriptive study of Italian teenagers from high schools in Rome who wear CL. We inquired about the different aspects of CL care through a questionnaire. RESULTS: We investigated 3,106 students from high schools in Rome (2% of all Roman high school students), 293 of whom wore CL (9%); 151 (52%) of participants responded, 42 (27.8%) male and 109 (72.8%) female. The mean age was 16.4 ± 1.6 years. 79.5% of students were daily users. 45.7% wore CL more than nine hours/day. 87.4% wore soft CL. 33.1% wore disposable CL; 7.9% weekly CL, 55% monthly CL. Thirty-four percent wore disposable lenses twice or more. 14.5% of students did not wash their hands before handling CL and 52.3% wore CL after it had fallen in the sink. 39.7% rubbed and cleaned CL before storing it. 10% used expired lens care solutions. Only 31.1% changed CL cases every three months. 38.4% wore CL in a swimming pool. 61.6% were having problems: redness (13.9%), itching (7.9%), and foreign body sensation (29.1%). CONCLUSION: Many students don't properly care for their CL. Education regarding proper care and management of CL among users is advised in view of frequency of symptoms and complications reported.

Follow-Up Study of Over Three Years of Patients with Uveitis after Cataract Phacoemulsification: Outcomes and Complications.

PURPOSE: To evaluate the rate and onset of intraoperative and postoperative complications post-phacoemulsification. METHODS: One hundred sixty-two eyes of 145 patients with uveitis who underwent phacoemulsification between 2006 and 2009 were identified through surgical record review. Fifty-nine eyes of 46 patients met the inclusion criteria. Hazard ratio (HR) and Kaplan-Meier survival probability were calculated for each class of uveitis. RESULTS: Macular edema (ME) resulted to be associated to chronic postoperative inflammation (r = 0.6; p = 0.00) and mostly related to patients who presented more than one postoperative relapse/year (r = 0.2; p = 0.02). Fuchs uveitis resulted to be a risk factor for posterior capsule opacification (PCO) (HR 3.36 IC95%1.0-10.5; p = 0.03). Hypotony and elevated intraocular pressure (IOP) were detected in the anterior uveitis group (0.02 EY). CONCLUSION: The HR to develop ME was significantly related to chronic anterior uveitis. PCO and elevated IOP are most frequent in Fuchs uveitis. The postoperative visual acuity result was good among all the uveitis groups.

Spectral domain optical coherence tomography imaging of tubercular chorioretinitis and intraretinal granuloma. Intraretinal tuberculosis: a case report.

The aim of this study is to report the clinical and spectral domain optical coherence tomography (SD-OCT) findings in a patient suffering from ulcerative colitis with bilateral tubercular chorioretinitis and intraretinal granuloma regressed with systemic antitubercular therapy (ATT). This study is a case report of a 33-year-old Bangladeshi male with ulcerative colitis treated with oral corticosteroids and azathioprine who was referred to our department with a diagnosis of central serous chorioretinopathy. Serological tests, the Mantoux skin test, complete ophthalmologic examination, ocular fundus photography, fundus fluorescein angiography, and SD-OCT scans were performed. The ophthalmological inflammatory pattern and serological investigations provided an early diagnosis of ocular tuberculosis. Systemic ATT led to significant improvement and resolution of the ocular inflammation. SD-OCT was a useful non-contact imaging technique in the follow-up of tubercular choroiditis. The excellent response to systemic ATT confirmed the clinical diagnosis. This is an unusual case of tubercular chorioretinitis with intraretinal granuloma and is the first such SD-OCT description reported in the ophthalmological literature.

Laser in situ keratomileusis for -6.00 to -18.00 diopters of myopia and up to -5.00 diopters of astigmatism: 15-year follow-up.

PURPOSE: To evaluate the long-term outcomes of laser in situ keratomileusis (LASIK) for high myopia with or without astigmatism. SETTING: Vissum Instituto Oftalmologico de Alicante and Miguel Hernandez University, Alicante, Spain. DESIGN: Retrospective-prospective case series. METHODS: Laser in situ keratomileusis was performed using the Visx 20/20 excimer laser. The minimum follow-up was 15 years. The main outcome measures were uncorrected (UDVA) and corrected (CDVA) distance visual acuities, manifest refraction, and corneal topography. RESULTS: This study included 40 patients (40 eyes) with a mean age of 51.08 years ± 6.67 (SD) (range 41 to 60 years) with high myopia (-6.00 to -18.00 diopters [D]). At 15 years, the safety index was 1.23 and the efficacy index, 0.95. During the follow-up, a significant increase in the dioptric power of all keratometric variables was detected (P≤.028, Friedman test), the most notable increase occurring between 3 months and 1 year (P≤.005). At 15 years, 46.15% of the eyes were within ±1.00 D of the attempted spherical equivalent and 64.10% were within ±2.00 D. The UDVA at 15 years was 20/25 or better in 43.59% of eyes and 20/40 or better in 64.10% of eyes. The postoperative CDVA was significantly better than preoperatively (P<.001). The postoperative complications were minor except in 1 eye in which ectasia occurred. CONCLUSIONS: Laser in situ keratomileusis for high myopia was safe over the long term. However, significant myopic regression with time was detected. Low preoperative pachymetry and low residual stromal bed were predictors of keratometric regression. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.