Keratoconus Progression in Patients With Allergy and Elevated Surface Matrix Metalloproteinase 9 Point-of-Care Test.

PURPOSE: To assess keratoconus (KC) progression in patients with allergies who also tested positive to surface matrix metalloproteinase 9 (MMP-9) point-of-care test. METHODS: Prospective comparative study including 100 stage I-II keratoconic patients, mean age 16.7±4.6 years. All patients underwent an anamnestic questionnaire for concomitant allergic diseases and were screened with the MMP-9 point-of-care test. Patients were divided into two groups: patients KC with allergies (KC AL) and patients KC without allergies (KC NAL). Severity of allergy was established by papillary subtarsal response grade and KC progression assessed by Scheimpflug corneal tomography, corrected distance visual acuity (CDVA) measurement in a 12-month follow-up. RESULTS: The KC AL group included 52 patients and the KC NAL group 48. In the KC AL group, 42/52 of patients (81%) were positive to MMP-9 point-of-care test versus two positive patients in the KC NAL group (4%). The KC AL group data showed a statistically significant decrease of average CDVA, from 0.155±0.11 to 0.301±0.2 logarithm of the minimum angle of resolution (P<0.005) at 12 months; Kmax value increased significantly, from 50.2 D±2.7 to 55.2 D±1.9 on average. The KC NAL group revealed a slight KC progression without statistically significant changes. Pearson correlation test showed a high correlation between Kmax worsening and severity of PSR in the KC AL group. CONCLUSIONS: The study demonstrated a statistically significant progression of KC in patients with concomitant allergies, positive to MMP-9 point-of-care test versus negative. A high correlation between severity of allergy and KC progression was documented.

CD93 as a Potential Target in Neovascular Age-Related Macular Degeneration.

In patients with age-related macular degeneration (AMD), choroidal neovascularization is the major cause of severe visual loss. In these patients, the persistence of neovascular growth despite vascular endothelial growth factor-A blockage needs the discovery of new endothelial cell targets. The glycoprotein CD93, highly expressed in activated endothelial cells, has been recently involved in the regulation of the angiogenic process both as transmembrane and soluble protein. Choroidal neovascular membranes from patients affected by AMD were examined by immunofluorescence using anti-CD93 and anti-von Willebrand factor antibodies. Blood vessels within intraocular and extraocular neoplasias were used as controls for CD93 expression. All choroidal neovascular membranes displayed strong CD93 staining in the von Willebrand factor-positive endothelial cells, consistently with the analyses showing a high colocalization coefficient in the blood vessels. Intraocular and extraocular tumor vessels showed similar results, whereas the normal choroid displayed blood vessels with only faint CD93 staining. Additionally, the concentration of soluble CD93 was determined in the aqueous humor of patients affected by naïve neovascular AMD by enzyme-linked immunosorbent assays. Age-matched cataract patients served as controls. Soluble CD93 was significantly increased in the aqueous humor of naïve neovascular AMD patients and tended to decrease after treatment with an antiangiogenic drug. In conclusion, both transmembrane and soluble CD93 are overexpressed in patients with neovascular AMD, indicating that CD93 may represent a potential new antiangiogenic target in the treatment of choroidal neovascularization. J. Cell. Physiol. 232: 1767-1773, 2017. © 2016 Wiley Periodicals, Inc.

Forty-two-month outcome of intravitreal bevacizumab in myopic choroidal neovascularization.

PURPOSE: To evaluate the long-term efficacy of bevacizumab in the treatment of choroidal neovascularization (CNV) secondary to pathological myopia. METHODS: In this retrospective single-center non-comparative study the medical records of 29 eyes from 29 patients with naïve CNV secondary to high myopia and at least 42 months of follow up were reviewed. All eyes received a loading dose of one intravitreal injection per month for two consecutive months and were retreated on an as-needed basis during the course of follow up. The main outcome measures were post-treatment ETDRS best-corrected visual acuity (BCVA) and visual stabilization over time. Stepwise linear regression analysis was performed to identify prognostic factors for visual acuity gain and final visual acuity outcome at 42 months. RESULTS: At 42 months of follow-up bevacizumab was associated with the maintenance of significant benefits in visual acuity compared to baseline. No adverse ocular or systemic effects from treatment were encountered. No statistically significant correlations were found between BCVA change and any of the quantitative variables. However, when final BCVA was taken as a dependent variable and CNV size and pre-treatment VA were included as predictors, a bivariate model was identified by stepwise regression which gave a 75 % of explained variance. CONCLUSIONS: Bevacizumab treatment was found to be efficacious in the treatment of myopic CNV, resulting in stable gains in visual acuity lasting at least 42 months, without any adverse ocular or general events. Myopic CNV size was identified as a significant prognostic factor.

Treatment of macular edema because of occlusive vasculitis with bevacizumab (avastin): efficacy of three consecutive monthly injections.

PURPOSE: To report the efficacy of intravitreal bevacizumab, administered in a series of three monthly injections followed by a period of observation, in the treatment of cystoid macular edema because of occlusive vasculitis. METHODS: This is a retrospective review of 13 consecutive eyes of 13 patients with cystoid macular edema because of occlusive vasculitis, which had been unresponsive to other medications and were treated with intravitreal bevacizumab (1.25 mg). The evaluation consisted of a complete ophthalmologic examination, including best-corrected visual acuity measurement, ophthalmoscopy, fluorescein angiography, and optical coherence tomography. The eyes received a series of 3 monthly injections followed by a 3-month observation period. RESULTS: A significant improvement in foveal thickness and visual acuity was obtained after the first injection, which increased after the second and the third injections and was maintained for 1.5 months after the last injection. The 2 parameters returned to the baseline values 3 months after the last treatment. There were no ocular or systemic adverse effects. CONCLUSION: Intravitreal injection of bevacizumab seems to be well tolerated and is associated with short-term improvement of visual acuity and decreased retinal thickness in patients with cystoid macular edema because of vasculitis that is resistant to conventional therapy.

Rifabutin corneal deposits in a patient with acquired immunodeficiency syndrome: in vivo confocal microscopy investigation.

PURPOSE: To establish the real localization of rifabutin-related corneal deposits in a patient with human immunodeficiency virus (HIV) infection by in vivo HRT II confocal microscopy with related clinicopathologic implications. METHODS: Observational case report. After Siena University Institutional Review Board approval in May 2008 and specific informed consent, a 54-year-old patient with HIV infection under rifabutin treatment for acquired immunodeficiency syndrome-related Mycobacterium avium complex prevention who developed diffuse corneal deposits was examined at the Department of Ophthalmology of Siena University. He underwent a complete clinical eye examination, biomicroscopy, and digital slit lamp photographs, endothelial specular microscopy, ultrasound pachymetry, and confocal microscopy by HRT II system. RESULTS: Confocal scans revealed the presence of deep stromal and pre descemetic hyperreflective polymorphous deposits. In vivo confocal examination excluded the presence of rifabutin-related deposits at endothelial level. CONCLUSIONS: Confocal microscopy enables establishment of the real localization of rifabutin deposits at deep stromal level, providing a better qualitative analysis of all corneal layers compared to biomicroscopic examination, with clinical and physiopathologic implications.

In vivo confocal microscopy in a patient with conjunctival lymphoma.

A case of primary conjunctival mucosa-associated lymphoid tissue lymphoma studied by in vivo corneal confocal microscopy (IVCM) is described for the first time. Examination of the lower mediobulbar and forniceal conjunctiva of the left eye of a 37-year-old female patient showed a typical salmon-pink patch. IVCM examination of the conjunctival lesion showed irregular, polygonal, conjunctival bulbar epithelial cells with blurred edges and without visible nucleus. Many small, roundish, hyper-reflective cells were also seen. These cells were arranged diffusely or in nests in cyst-like hypo-reflective spaces. A few highly reflective cells were also visible among deep stromal collagen fibres. The IVCM picture recalled the histological profile of low-grade mucosa-associated lymphoid tissue lymphoma, characterized by sheets of neoplastic cells around reactive follicles. IVCM enabled non-invasive evaluation of the eye surface at high magnification and with good contrast, and could be useful for early differential diagnosis of conjunctival lesions.

Fractal analysis of fluoroangiographic patterns in anterior ischaemic optic neuropathy and optic neuritis: a pilot study.

BACKGROUND: To evaluate by means of fractal analysis the vascular pattern of the optic nerve head obtained by fluorescein angiogram, in non-arteritic anterior ischaemic optic neuropathy (NAION) and optic neuritis (ON). METHODS: Twenty-nine patients at the Department of Ophthalmology of the University of Siena, diagnosed as having either NAION or ON by clinical and instrumental criteria, were prospectively subjected to fractal analysis: 11 patients with NAION and 18 patients with ON. In the ON group, 12 patients showed optic disc oedema, whereas six patients showed no optic disc oedema. The unaffected eyes of six patients with NAION and of seven patients with ON associated with optic disc oedema served as controls. RESULTS: The mean fractal dimension D was 1.84 +/- 0.09 in the NAION group, 1.92 +/- 0.04 in the ON group with optic disc oedema, 1.86 +/- 0.04 in the ON group without optic disc oedema and 1.63 +/- 0.06 in the control group; all case groups showed significantly higher values than controls (P < 0.01). Among the case groups, the ON group with optic disc oedema showed a significantly higher mean fractal dimension value than the others (P < 0.01). CONCLUSIONS: Our data suggest that eyes with ON and NAION seem to have increased vascular complexity in the optic nerve head, manifested as an increase in fractal dimension.

Corneal Subbasal Nerve Density and Sensitivity After Pars Plana Vitrectomy Using Contact or Noncontact Wide-Angle Viewing Systems.

PURPOSE: To assess corneal subbasal nerve density (SBND) and corneal sensitivity (CS) after pars plana vitrectomy (PPV) for rhegmatogenous retinal detachment (RRD) without intraoperative 360-degree laser treatment using contact or noncontact panoramic viewing systems. METHODS: This is a prospective study of 34 eyes affected by RRD, which underwent PPV using contact (18 eyes) and noncontact (16 eyes) panoramic viewing systems; 12 eyes which underwent scleral buckling, and 17 eyes which underwent cataract surgery. SBND and CS were assessed before surgery and 3 and 6 months postoperatively by in vivo confocal microscopy and Cochet-Bonnet esthesiometry. RESULTS: Compared with baseline values, at 6 months, SBND and CS decreased in both contact PPV (SBND preoperative value: 19.1 ± 3.7 mm/mm; SBND postoperative value: 3.5 ± 1.3 mm/mm; CS preoperative value: 5.1 ± 0.5 cm; CS postoperative value: 1.5 ± 0.4 cm) and in noncontact PPV groups (SBND preoperative value: 19.5 ± 3.8 mm/mm; SBND postoperative value: 8.7 ± 2.3 mm/mm; CS preoperative value: 5.3 ± 0.5 cm; CS postoperative value: 2.5 ± 0.7 cm) (P < 0.001 for all comparisons). SBND reduction was greater in the contact PPV group than in the noncontact PPV group (P < 0.001). By contrast, the scleral buckling and cataract surgery group values were unchanged (P > 0.1 for all comparisons). In multivariate analysis, no significant effect was found for cataract surgery associated with PPV, pseudophakia, surgical time, intraocular pressure, or for laser in horizontal sectors for PPV groups. SBND was highly correlated with CS (r = 0.93). CONCLUSIONS: A contact viewing system reduces SBND after PPV more than a noncontact system does.

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.

Publisher Correction: TGF-ß concentrations and activity are down-regulated in the aqueous humor of patients with neovascular age-related macular degeneration.

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TGF-ß concentrations and activity are down-regulated in the aqueous humor of patients with neovascular age-related macular degeneration.

Controversy still exists regarding the role of the TGF-ß in neovascular age-related macular degeneration (nAMD), a major cause of severe visual loss in the elderly in developed countries. Here, we measured the concentrations of active TGF-ß1, TGF-ß2, and TGF-ß3 by ELISA in the aqueous humor of 20 patients affected by nAMD, who received 3 consecutive monthly intravitreal injections of anti-VEGF-A antibody. Samples were collected at baseline (before the first injection), month 1 (before the second injection), and month 2 (before the third injection). The same samples were used in a luciferase-based reporter assay to test the TGF-ß pathway activation. Active TGF-ß1 concentrations in the aqueous humor were below the minimum detectable dose. Active TGF-ß2 concentrations were significantly lower at baseline and at month 1, compared to controls. No significant differences in active TGF-ß3 concentration were found among the sample groups. Moreover, TGF-ß pathway activation was significantly lower at baseline compared to controls. Our data corroborate an anti-angiogenic role for TGF-ß2 in nAMD. This should be considered from the perspective of a therapy using TGF-ß inhibitors.

Treatment of progressive keratoconus by riboflavin-UVA-induced cross-linking of corneal collagen: ultrastructural analysis by Heidelberg Retinal Tomograph II in vivo confocal microscopy in humans.

PURPOSE: To assess ultrastructural stromal modifications after riboflavin-UVA-induced cross-linking of corneal collagen in patients with progressive keratoconus. METHODS: This was a second-phase prospective nonrandomized open study in 10 patients with progressive keratoconus treated by riboflavin-UVA-induced cross-linking of corneal collagen and assessed by means of Heidelberg Retinal Tomograph II Rostock Corneal Module (HRT II-RCM) in vivo confocal microscopy. The eye in the worst clinical condition was treated for each patient. Treatment under topical anesthesia included corneal deepithelization (9-mm diameter) and instillation of 0.1% riboflavin phosphate-20% dextran T 500 solution at 5 minutes before UVA irradiation and every 5 minutes for a total of 30 minutes. UVA irradiation was 7 mm in diameter. Patients were assessed by HRT II-RCM confocal microscopy in vivo at 1, 3, and 6 months after treatment. RESULTS: Rarefaction of keratocytes in the anterior and intermediate stroma, associated with stromal edema, was observed immediately after treatment. The observation at 3 months after the operation detected keratocyte repopulation in the central treated area, whereas the edema had disappeared. Cell density increased progressively over the postoperative period. At approximately 6 months, keratocyte repopulation was complete, accompanied by increased density of stromal fibers. No endothelial damage was observed at any time. CONCLUSIONS: Reduction in anterior and intermediate stromal keratocytes followed by gradual repopulation has been confirmed directly in vivo in humans by HRT II-RCM confocal microscopy after riboflavin-UVA-induced corneal collagen cross-linking.

HTRA1 and TGF-ß1 Concentrations in the Aqueous Humor of Patients With Neovascular Age-Related Macular Degeneration.

Purpose: The purpose of this study was to evaluate the expression of high-temperature requirement A serine peptidase 1 (HTRA1), TGF-ß1, bone morphogenetic protein 4 (BMP4), growth differentiation factor 6 (GDF6), and VEGFA proteins in the aqueous humor of patients with naïve choroidal neovascularization (nCNV) secondary to AMD. Methods: We measured by ELISA the concentrations of HTRA1, TGF-ß1, BMP4, GDF6, and VEGFA in the aqueous humor of 23 patients affected by nCNV who received three consecutive monthly intravitreal injections of 0.5 mg ranibizumab. Samples were collected at baseline (before the first injection), month 1 (before the second injection), and month 2 (before the third injection). Twenty-three age-matched cataract patients served as controls. Results: Bone morphogenetic protein 4 and GDF6 were not detectable in any samples. Baseline HTRA1 was higher than controls (P < 0.0001) and higher than both the month 1 (P < 0.0001) and the month 2 (P < 0.0001) values. Baseline VEGFA was higher than controls (P < 0.0001), not different from month 1 value (P = 0.0821), but higher than month 2 value (P < 0.0001). Baseline TGF-ß1 was higher than controls (P = 0.0015) and not different from month 1 (P = 0.129) and month 2 values (P = 0.5529). No correlation was found in naïve patients between concentrations of HTRA1 and TGF-ß1, HTRA 1 and VEGFA, or TGF-ß1 and VEGFA. Conclusions: In nCNV patients, HTRA1 and TGF-ß1 were significantly higher compared to controls. After treatment, TGF-ß1 was persistently elevated, while HTRA1 returned to control levels, suggesting the involvement of TGF-ß1 and HTRA1 in neovascular AMD and a VEGFA-independent role for TGF-ß1.

Parasurgical therapy for keratoconus by riboflavin-ultraviolet type A rays induced cross-linking of corneal collagen: preliminary refractive results in an Italian study.

PURPOSE: To assess the effectiveness of riboflavin-ultraviolet type A rays induced cross-linking of corneal collagen in reducing progression of keratoconus and in improving visual acuity in patients with progressive keratoconus. SETTING: Department of Ophthalmology, Siena University, Siena, Italy. METHODS: This was a second-phase prospective nonrandomized open study. Starting in September 2004, 10 eyes of 10 patients (mean age 31.4 years) with bilateral keratoconus were treated by combined riboflavin-ultraviolet type A rays (UVA) collagen cross-linking. Radiant energy was 3 mW/cm2 or 5.4 joule/cm2 for a 30-minute exposure at 1 cm from the corneal apex. A complete ophthalmologic examination (uncorrected visual acuity [UCVA], sphere spectacles corrected visual acuity (SSCVA), best spectacle-corrected visual acuity [BSCVA]) was performed. Patients had corneal computerized topographic examination, linear scan optical tomography, endothelial cell count, ultrasound pachometry, intraocular pressure (IOP) evaluation, and HRT II system confocal microscopy at 1, 2, 3, and 6 months. After treatment, eyes were medicated and dressed with a soft contact lens. RESULTS: Comparative preoperative and postoperative results showed increases of 3.6 lines for UCVA (P = .0000112), 1.85 lines for SSCVA (P = .00065), and 1.66 lines for BSCVA (P = .00071). Topographic analysis showed a mean K reduction of 2.1 +/- 0.13 diopters (D) in the central 3.0 mm. Statistical analysis of IOP and endothelial cell count did not show significant differences. Topo-aberrometric analysis findings of corneal symmetry showed a trend toward increasing corneal symmetry with a major reduction in asymmetry between vertical hemimeridians. CONCLUSIONS: Refractive results showed a reduction of about 2.5 D in the mean spherical equivalent, topographically confirmed by the reduction in mean K. Results of surface aberrometric analysis showed improvement in morphologic symmetry with a significant reduction in comatic aberrations.

Accelerated Corneal Collagen Cross-Linking Using Topography-Guided UV-A Energy Emission: Preliminary Clinical and Morphological Outcomes.

Purpose. To assess the clinical and morphological outcomes of topography-guided accelerated corneal cross-linking. Design. Retrospective case series. Methods. 21 eyes of 20 patients with progressive keratoconus were enrolled. All patients underwent accelerated cross-linking using an ultraviolet-A (UVA) exposure with an energy release varying from 7.2 J/cm2 up to 15 J/cm2, according to the topographic corneal curvature. Uncorrected (UDVA) and corrected (CDVA) distance visual acuity, topography, in vivo confocal microscopy (IVCM), and anterior segment optic coherence tomography (AS-OCT) were evaluated preoperatively and at the 1, 3, 6, and 12 months postoperatively. Results. 12 months after surgery UDVA and CDVA did not significantly vary from preoperative values. The average topographic astigmatism decreased from -4.61 ± 0.74 diopters (D) to -3.20 ± 0.81 D and coma aberration improved from 0.95 ± 0.03 µm to 0.88 ± 0.04 µm after surgery. AS-OCT and IVCM documented differential effects on the treated areas using different energies doses. The depths of demarcation line and keratocyte apoptosis were assessed. Conclusions. Preliminary results show correspondence between the energy dose applied and the microstructural stromal changes induced by the cross-linking at various depths in different areas of treated cornea. One year after surgery a significant reduction in the topographic astigmatism and comatic aberration was detected. None of the patients developed significant complications.

Entropy of corneal nerve fibers distribution observed by laser scanning confocal microscopy: A noninvasive quantitative method to characterize the corneal innervation in Sjogren's syndrome patients.

Sjogren's syndrome (SS) is a progressive autoimmune condition mainly affecting the salivary and lacrimal glands with an incidence of primary SS between 1/100 and 1/1,000. SS implies an alteration in the epithelium and subepithelium innervation, with consequent reduction of corneal sensitivity. It is necessary to have noninvasive quantitative methods to characterize the status of the corneal nerve fibers of the patients in order to choose and follow the best therapy. Entropy (information dimension) of the nerve corneal fibers distribution observed by confocal microscopy was evaluated in patients with primary SS (n = 30, 6 males, 24 females, 21-81 years), diagnosed by biopsy of salivary gland and blood tests and in sex- age-matched healthy subjects (n = 12). Corneal nerve fiber density, Langerhans cell count, and cell density in the nerve plexus images were also evaluated. In selected patients salivary gland atrophy degree was also evaluated. Nerve corneal distribution observed by confocal microscopy is fractal. Entropy of the corneal nerve distribution statistically distinguishes between SS patients and healthy subjects: patients present a lower value of information dimension of the corneal nerve fibers distribution than healthy individuals (P < 0.001). Percentage of grouped cases classified by entropy according to the subjects (selected patients vs. healthy) showed a 100% sensitivity and 96% specificity, P < 0.0001 with a low value of coefficient of variation among the individuals (6-7 times lower than the other morphometric indexes). Entropy correlated with the severity of the disease (salivary gland atrophy degree, P < 0.01). Evaluation of entropy of the corneal nerve distribution observed by a laser confocal microscopy appears to quantitatively and noninvasively characterize an aspect of the SS patients in relation to the recognition of an impairment of their ocular surface, giving us for the first time a method to objectively and precisely characterize the corneal innervation status in the SS patients.

Phenotypic Spectrum of Granular Corneal Dystrophy Type II in Two Italian Families Presenting an Unusual Granular Corneal Dystrophy Type I Clinical Appearance.

Clinical, instrumental, and genetic findings are reported in Italian families with Type II Granular Corneal Dystrophies (GCD2) presenting an initial unusual presentation of a Granular Corneal Dystrophy Type I (GCD1) phenotypic spectrum in female descendants. Slit-lamp examinations showed the typical phenotypic features of GCD2 in both mothers and a phenotypic appearance of GCD1 in both daughters. Despite the different phenotypic onset, the genetic diagnostic testing revealed the presence of a mutation in the TGFB-I gene, typical of GCD2 in both cases, excluding GCD1. Patients who were clinically suspected of corneal dystrophy need a genetic confirmatory testing for certain diagnosis. Genetic test may help to find the specific mutation distinguishing between different phenotypic spectra with relative diagnostic and prognostic implications. The study demonstrates that the phenotypic spectrum of genetically confirmed granular corneal dystrophies in patients may change over time. Since the R124H mutation has also been described in clinically asymptomatic individuals prior to LASIK, who then develop dramatic deposition, suggesting that this particular mutation and phenotype may be sensitive to, precipitated, or modified by central cornea trauma, a careful familial anamnesis excluding cornel dystrophies and specific preoperative genetic test are recommended prior to LASIK.

In Vivo Confocal Microscopy after Corneal Collagen Crosslinking.

In vivo confocal microscopy (IVCM) findings of 84 patients who had undergone conventional epithelium-off corneal collagen crosslinking (CXL) and accelerated CXL (ACXL) were retrospectively reviewed. Analysis confirmed that despite a significant decrease in the mean density of anterior keratocytes in the first 6 postoperative months, cell density after CXL and ACXL returned to baseline values at 12 months. The demarcation lines observed after treatments represent an expression of light-scattering (reflectivity changes) through different tissue densities. Temporary haze of the anterior-mid stroma after conventional CXL represents an indirect sign of CXL-induced stromal collagen compaction and remodeling. IVCM showed that treatment penetration varies to some extent, but that the endothelium is not damaged and is correlated with CXL biomechanical effects. IVCM of limbal structures shows no evidence of pathological changes. Regeneration of subepithelial and stromal nerves was complete 12 months after the operation with fully restored corneal sensitivity and no neurodystrophic occurrences. IVCM allowed detailed high magnification in vivo micromorphological analysis of corneal layers, enabling the assessment of early and late corneal modifications induced by conventional and accelerated CXL. IVCM confirms that CXL is a safe procedure, which is still undergoing development and protocol adjustments.

Bilateral dexamethasone intravitreal implant in a young patient with Vogt-Koyanagi-Harada disease and refractory uveitis.

Vogt-Koyanagi-Harada disease (VKHD) is a multisystemic disorder characterized by granulomatous panuveitis with exudative retinal detachments, often associated with neurologic and cutaneous manifestations. Therapy relies mainly on the use of corticosteroids, administrated as oral or intravenous high-dose pulses, and immunosuppressants. However, since macular edema and retinal detachment can often be refractory to systemic therapies, intravitreal triamcinolone acetate has been used successfully. Herein, we report the first case of refractory bilateral panuveitis in a young patient with VKHD successfully treated with dexamethasone intravitreal implant.