An in vivo confocal microscopy study of corneal changes in pseudoexfoliation syndrome.

PURPOSE: To evaluate, through the in vivo confocal microscopy, the pathological changes of each corneal layer in eyes affected by pseudoexfoliation syndrome. METHODS: We studied 40 eyes of 40 patients with diagnosis of unilateral senile cataract associated with pseudoexfoliation syndrome and 40 eyes of 40 control subjects with senile cataract without pseudoexfoliation syndrome. All patients underwent a complete ophthalmic examination including best corrected visual acuity, slit-lamp examination, corneal sensitivity measurement using a Cochet-Bonnet nylon thread esthesiometer, and anterior segment optical coherence tomography (Visante OCT, Carl Zeiss Meditec AG, Germany); in vivo confocal microscopy of corneal sections (endothelium, stroma, sub-basal nerve plexus, and superficial and basal epithelium) was performed with the ConfoScan 4.0 (Nidek, Japan). RESULTS: In pseudoexfoliation syndrome group, the mean corneal sensitivity was 44.1 ± 1.3 mm and in the control group was 55.6 ± 4.7 mm. The corneas of the eyes with pseudoexfoliation syndrome were significantly less sensitive than those of control group eyes (p < 0.001). Pseudoexfoliation syndrome eyes had a lower nerve density and less nerve beadings and a higher degree of tortuosity in sub-basal plexus compared to the control group. The cell density of epithelial and endothelial layers was significantly lower in pseudoexfoliation syndrome eyes than controls. In 80% of pseudoexfoliation syndrome eyes, we found activated keratocytes and inflammatory cells in the anterior stroma. CONCLUSION: Our study demonstrates the morpho-structural corneal alterations in eyes affected by pseudoexfoliation syndrome, using corneal in vivo confocal microscopy as a non-invasive and high-reproducible technique to evaluate pathophysiology of each corneal layer; the sub-basal nerve plexus alterations are correlated with the lower corneal sensitivity.

CFH Y402H polymorphism in Italian patients with age-related macular degeneration, retinitis pigmentosa, and Stargardt disease.

BACKGROUND: The complement system has been implicated in the pathogenesis of age-related macular degeneration (AMD) and the CFH Y402H polymorphism has been suggested as a major risk factor for AMD. Recent evidences supported the role of inflammation in the pathogenesis of some retinal dystrophies. Aim of this study was to evaluate the prevalence of CFHY402H polymorphism in a group of Italian patients affected by atrophic AMD, Stargardt disease (STGD), or retinitis pigmentosa(RP). MATERIALS AND METHODS: Our case-control association study included 116 patients with atrophic AMD, 77 with RP, 86 with STGD, and 100 healthy controls. All the patients were evaluated by a standard ophthalmologic examination and OCT. ERG was performed on STGD and RP patients. All the subjects underwent a blood drawing for genetic testing and the CFHY402H polymorphism was genotyped with the TaqMan real-time polymerase chain reaction single nucleotide polymorphism assay. RESULTS: The prevalence of the risk genotype C/C was higher in the AMD group than in controls (p < 0.001). The risk allele C was more frequent in the AMD group than in controls (p < 0.001). The prevalence of the risk genotype was higher in the RP patients than in controls (p < 0.001) and similarly the risk allele C was more frequent in the RP group (p = 0.008). The CFHY402H genotype distribution was not different between patients with STGD and the controls, for the biallelic (p = 0.531) and for the monoallelic (p = 0.318) evaluation. CONCLUSIONS: In our series of Italian patients, the CFHY402H genotype is associated with atrophic AMD and RP, but not with STGD. This result may support the hypothesis of a complement system dysregulation in the pathogenesis of AMD and RP.

Comparative analysis of visual outcomes, reading skills, contrast sensitivity, and patient satisfaction with two models of trifocal diffractive intraocular lenses and an extended range of vision intraocular lens.

PURPOSE: To compare visual and contrast sensitivity (CS) outcomes, reading skills, and spectacle independence in patients implanted with two models of trifocal intraocular lenses (IOLs) or an extended range of vision (ERV) IOL. METHODS: This non-randomized prospective series of cases included 120 eyes of 60 patients undergoing cataract surgery with bilateral implantation of three different IOLs: the ERV IOL Tecnis Symfony (40 eyes) (Abbott Medical Optics), the trifocal IOLs PanOptix IQ (40 eyes) (Alcon), and AT LISA tri 839MP (40 eyes) (Carl Zeiss Meditec). Visual results, photopic and mesopic CS, binocular reading skills (MNREAD charts), and patient satisfaction were evaluated 3 months after surgery. RESULTS: There was no statistically significant difference between groups regarding uncorrected and corrected distance visual acuity. The Tecnis Symfony IOL showed better mesopic intermediate visual outcomes than the two trifocal IOLs (p < 0.05 vs AT LISA). Under photopic conditions, AT LISA tri 839MP and PanOptix IQ showed better near visual outcomes compared with the ERV IOL (p < 0.05 to p < 0.001). The Tecnis Symfony IOL provided significantly better photopic and mesopic CS outcomes than the other IOL models (p < 0.001). Reading skills were not significantly different between the three IOL models (p > 0.05). Less patients implanted with the two trifocal IOLs required a near addition than patients with the ERV IOL. CONCLUSIONS: All the tested IOLs provided good visual outcome, reading performance, and spectacle independence after cataract surgery. While trifocal IOLs gave better near visual acuity results, the ERV IOL provided better contrast sensitivity.

Corneal Collagen Cross-Linking With Riboflavin and Ultraviolet A Light for Pediatric Keratoconus: Ten-Year Results.

PURPOSE: To assess the 10-year follow-up efficacy and safety of riboflavin ultraviolet A-induced cross-linking (CXL) in a population of pediatric patients aged 18 years and younger with progressive keratoconus (KC). METHODS: The prospective longitudinal cohort study included 62 eyes of 47 keratoconic patients undergoing epithelium-off CXL who completed 10-year follow-up. The surgical procedure was performed in all patients according to the Siena (Dresden modified) protocol. Evaluation included uncorrected distance visual acuity, corrected distance visual acuity, Scheimpflug corneal tomography, and optical coherence tomography demarcation line measurement. Follow-up measurements taken up to 10 years after treatment were compared with baseline values, and statistical analysis was performed using a 2-tailed paired sample Student t test. RESULTS: Uncorrected distance visual acuity and corrected distance visual acuity improved from 0.45 to 0.23 logarithm of the minimum angle resolution (P = 0.0001) and from 0.14 to 0.1 logarithm of the minimum angle resolution (P = 0.019). KC stability was recorded after 10 years of follow-up in nearly 80% of the patients. The overall 10-year follow-up progression rate was 24% including 13 eyes of 9 patients with Kmax progression over 1 diopter and 2 eyes of 2 patients who underwent corneal grafting. CONCLUSIONS: The study demonstrates the ability of CXL to slow down KC progression in pediatric patients, improving functional performance. Long-term stability may be correlated with CXL-induced delay in corneal collagen turnover and with spontaneous age-related KC stabilization. A 24% regression rate could be contemplated in the patients who were aged 15 years and younger at the time of inclusion in the treatment protocol.

EDI OCT evaluation of choroidal thickness in Stargardt disease.

PURPOSE: Choroidal thickness (CT) evaluation with EDI-OCT in Stargardt Disease (STGD), considering its possible association with some clinical features of the disease. METHODS: CT was evaluated in 41 STGD patients and in 70 controls. Measurements were performed in the subfoveal position and at 1000 µm nasally and temporally. CT average values in STGD and in the control group were first compared by means of Student's T test. Then, the possible association between CT and some clinical features was evaluated by means of linear regression analysis. Considered clinical parameters were: age, age on onset, duration of the disease, visual acuity, foveal thickness, Fishman clinical phenotype, visual field loss and ERG response. RESULTS: Average CT was not significantly different between controls and STGD patients. In the STGD group the correlation between CT and age (r = 0.22, p = 0.033) and age of onset (r = 0.05, p = 0.424) was modest, while that of CT with disease duration (r = 0.30, p<0.001) was moderate. CT and foveal thickness were also significantly but modestly correlated (r = 0.15, p = 0.033). CONCLUSION: In our series average CT is not significantly changed in STGD in comparison with the controls. Nevertheless a choroidal thinning may be identified in the more advanced stages of the disease.

EDI-OCT evaluation of choroidal thickness in retinitis pigmentosa.

PURPOSE: To evaluate choroidal thickness (CT) in retinitis pigmentosa (RP) using enhanced depth imaging (EDI) optical coherence tomography (OCT). METHODS: A retrospective analysis of a group of patients with RP who underwent EDI-OCT was performed. Choroidal thickness measurements were compared with those of age- and sex-matched healthy subjects. In the RP group, the possible association between subfoveal CT and some clinical parameters (visual acuity, age, age at disease onset, duration of the disease, macular thickness, visual field loss, electroretinography [ERG]) was evaluated. RESULTS: The study recruited 39 patients with RP with an average age of 43.3 ± 11.3 years while the control group consisted of 73 healthy subjects with an average age of 42.9 ± 12.10 years. On average, CT was significantly thinner in the RP group compared to the controls (p<0.0001). In the RP group, we could not find any significant association between CT and the considered clinical parameters even if there was a trend for decreasing CT with increasing age (r = -0.23, p = 0.096). In the control group, subfoveal CT showed a slightly significant correlation with age (r = -0.21, p = 0.04) but not with macular thickness and visual acuity. CONCLUSIONS: In our series, CT was significantly lower in the RP group in comparison with the controls, as measured by EDI-OCT, but did not correlate with age, age at onset, duration of the disease, macular thickness, visual acuity, visual field loss, or ERG responses. Although the clinical implications of choroidal changes in RP have not yet been clearly determined, the evaluation of choroidal features may provide information that could be useful to clarify the pathophysiology of the disease.

Visual performance, reading ability and patient satisfaction after implantation of a diffractive trifocal intraocular lens.

PURPOSE: To evaluate visual outcome, reading performance, contrast sensitivity, and patient satisfaction after cataract surgery with implantation of a diffractive trifocal intraocular lens (IOL). PATIENTS AND METHODS: A total of 42 eyes (21 patients) underwent cataract surgery with implantation of the trifocal IOL AT LISA tri 839MP. Visual acuity, contrast sensitivity, and patient satisfaction were evaluated 3 months postoperatively. Reading performance was evaluated at 3 months postoperatively with the MNREAD charts. RESULTS: All eyes achieved a 3-month postoperative monocular uncorrected distance visual acuity of 0.10 logMAR or better (Snellen 20/25). Likewise, 97.62% and 85.71% of eyes achieved a postoperative monocular uncorrected intermediate, and near visual acuity of 0.20 logMAR (Snellen 20/30) or better. All patients achieved postoperative binocular uncorrected distance visual acuity, uncorrected intermediate, and uncorrected near visual acuity of 0.20 logMAR (Snellen 20/30) or better. Mean photopic reading acuity and speed were 0.24±0.07 logMAR and 177.61±20.67 words per minute, respectively. Postoperative contrast sensitivity values were within the ranges of normality for all spatial frequencies evaluated. Postoperative spectacle independence and patient satisfaction was very high, with most of the patients reporting a good or very good visual quality at far, intermediate, and near distances. All patients would choose the same lens again. CONCLUSION: The evaluated trifocal IOL provides an effective restoration of the visual function after cataract surgery, with high levels of distance, intermediate, and near visual acuity, strong reading performance, and patient satisfaction.

COMPUTER ASSISTED RETINAL VESSEL TORTUOSITY EVALUATION IN NOVEL MUTATION FABRY DISEASE: Towards New Prognostic Markers.

PURPOSE: Fabry disease is a rare lysosomal storage disorder with systemic involvement. The authors report on a large Fabry family with GLA p.M187R mutation and exhaustive ophthalmologic assessment. METHODS: Comprehensive systemic evaluation and genetic diagnosis were performed. Ophthalmologic evaluation included intraocular pressure/visual acuity measurement, refractometry, slit lamp examination, retinography, and optical coherence tomography. Three parameters quantified retinal vessel tortuosity: sum of angle metrics, product of angle distance, and triangular index. Calculations were semiautomatized using dedicated software. RESULTS: Ten individuals (2 males and 8 females) were described. Seventy-five percent had retinal vessel tortuosity. One hundred percent had cornea verticillata. Perimacular vessels were predominantly involved. The correlation between the right and left eye tortuosity measurements was very tight. A significant correlation between retinal vessel tortuosity and systemic severity measured by general Mainz Severity Score Index (MSSI), renal MSSI, and neurological MSSI but no cardiac MSSI was observed. Right sum of angle metrics value was an independent statistical predictor of the general-MSSI score in presence of age. CONCLUSION: p.M187R mutation causes a severe systemic and ophthalmologic phenotype, in both male and female patients. Semiautomatic assessment of retinal vessel tortuosity is an objective and reproducible tool. All three parameters of tortuosity are closely associated with Fabry severity scores. Studies of larger series are being awaited to establish the role of retinal vessel tortuosity as a noninvasive marker of disease progression.

En face OCT in Stargardt disease.

PURPOSE: To evaluate the structural features of the macular region by enface OCT imaging in patients with clinical diagnosis of Stargardt disease, confirmed by the detection of ABCA4 mutations. METHODS: Thirty-two STGD patients were included in the study for a total of 64 eyes. All patients received a comprehensive ophthalmological examination, color fundus photography, fundus auto-fluorescence imaging and OCT. Five OCT scans were considered: ILM and RPE scans (both automatically obtained from the instrument), above-RPE slab, photoreceptor slab and sub-RPE slab (these last three manually obtained). RESULTS: ILM scans showed evident radial folds on the retinal surface in 8/64 eyes (12.5 %). In 6 of the 7 patients, these vitreo-retinal interface abnormalities were unilateral. The photoreceptor slab showed some macular alterations ranging from dis-homogeneous, hypo-reflective abnormalities (7/64 eyes, 11 %) to a homogeneous, well-defined, roundish, hypo-reflective area (17/64 eyes, 27 %) in all the eyes. The sub-RPE slab showed a centrally evident, hyper-reflective abnormality in 58/64 eyes (90.6 %). Superimposing the sub-RPE slab over the images corresponding to the photoreceptor slab, the area of the photoreceptor atrophy sharply exceeded that of the RPE atrophy (44/46 eyes, 96 %). CONCLUSION: Enface OCT proved to be a clinically useful tool for the management of STGD patients, illustrating in vivo the structural abnormalities of the different retinal layers.

Long-Term Results of Photodynamic Therapy for Choroidal Neovascularization in Pediatric Patients with Best Vitelliform Macular Dystrophy.

PURPOSE: To report long-term results of photodynamic therapy (PDT) in young patients affected by Best vitelliform macular dystrophy (VMD) complicated by choroidal neovascularization (CNV). METHODS: We evaluated a group of 30 VMD patients with confirmed mutations in the BEST1 gene. Five of these patients had been diagnosed with CNV when younger than 15 years of age and three of them were treated by PDT. After the treatment they were followed for an average period of 77 months (range 62-99). RESULTS: In all the treated eyes visual acuity was stable during the first year of follow-up and then slowly improved even some years after the treatment. The improvement in visual acuity was associated with the development of fibrous tissue in the macula. CONCLUSIONS: PDT was a safe procedure in our series of pediatric patients with VMD complicated by CNV. It was followed by a CNV regression and a consequent improvement in visual acuity which continued to progress even several years after the treatment.

Corneal healing after riboflavin ultraviolet-A collagen cross-linking determined by confocal laser scanning microscopy in vivo: early and late modifications.

PURPOSE: To assess early and late micromorphological modifications of cross-linked corneas in vivo by means of Heidelberg Retinal Tomography (HRT) II confocal microscopy. DESIGN: Prospective nonrandomized open trial. METHODS: Micromorphological examination of 44 cross-linked keratoconic corneas was performed in vivo by HRT II confocal laser scanning microscopy. Riboflavin ultraviolet (UV)-A-induced corneal collagen cross-linking (CXL) was performed according to the Siena protocol: pilocarpin 1% drops 30 minutes before, topical anesthesia with lidocaine 4% drops 15 minutes before irradiation, mechanical scraping of epithelium (9-mm-diameter area), preirradiation soaking for 10 minutes in riboflavin solution 0.1% (Ricrolin, Sooft, Italy) applied every 2.5 minutes for 30 minutes, 30 minutes exposure to solid-state UVA illuminator (Caporossi; Baiocchi; Mazzotta, X-linker, CSO, Italy), 8-mm-diameter irradiated area, energy delivered 3 mW/cm(2). All patients were examined by confocal scans preoperatively and at the following times after treatment: one, three, and six months, and one, two, and three years. RESULTS: No damage to the limbal region was observed. Epithelial regrowth was complete after four days of soft contact lens bandage. The anatomy of the subepithelial plexus was restored one year after the operation with full corneal sensitivity. Increased density of extracellular matrix in late postoperative period indicated cross-linked collagen to a depth of 340 microm expressed by a late demarcation line. CONCLUSION: In vivo confocal microscopy showed early and late modification of corneal microstructure after the treatment. The three-year stability of CXL recorded could be related to increased cross-links formation, synthesis of well-structured collagen and new lamellar interconnections.

Confocal microscopy identification of keratoconus associated with posterior polymorphous corneal dystrophy.

We present a case of keratoconus in which the association with posterior polymorphous corneal dystrophy was established by confocal microscopy. Confocal microscopy enable us to assess the differential diagnosis between posterior corneal dystrophies, essential for a prognosis and therapeutic decision.