A Chronic Ocular-Hypertensive Rat Model induced by Injection of the Sclerosant Agent Polidocanol in the Aqueous Humor Outflow Pathway.

BACKGROUND: To induce a moderate chronic ocular hypertension (OHT) by injecting polidocanol, a foamed sclerosant drug, in the aqueous humor outflow pathway. METHODS: Intraocular pressure (IOP) was monitored for up to 6 months. Pattern and full-field electroretinogram (PERG and ERG) were recorded and retinal ganglion cells (RGC) and retinal nerve fiber layer (RNFL) thickness were assessed in vivo with optical coherence tomography (OCT) and ex vivo using Brn3a immunohistochemistry. RESULTS: In the first 3 weeks post-injection, a significant IOP elevation was observed in the treated eyes (18.47 ± 3.36 mmHg) when compared with the control fellow eyes (12.52 ± 2.84 mmHg) (p < 0.05). At 8 weeks, 65% (11/17) of intervention eyes had developed an IOP increase >25% over the baseline. PERG responses were seen to be significantly reduced in the hypertensive eyes (2.25 ± 0.24 µV) compared to control eyes (1.44 ± 0.19 µV) (p < 0.01) at week 3, whereas the ERG components (photoreceptor a-wave and bipolar cell b-wave) remained unaltered. By week 24, RNFL thinning and cell loss in the ganglion cell layer was first detected (2/13, 15.3%) as assessed by OCT and light microscopy. CONCLUSIONS: This novel OHT rat model, with moderate levels of chronically elevated IOP, and abnormal PERG shows selective functional impairment of RGC.

The S1P1 receptor-selective agonist CYM-5442 protects retinal ganglion cells in endothelin-1 induced retinal ganglion cell loss.

We investigated the feasibility and efficacy of using a specific sphingosine 1-phosphate (S1P1) receptor agonist, CYM-5442, to slow or block retinal ganglion cell (RGC) loss in endothelin-1 (ET-1) induced RGC loss. A single intravitreal injection of ET-1 (20pmol/ul), a potent vasoactive peptide that produces retinal vessels vasoconstriction, was used to induce and characterize RGC-specific cell death. CYM-5442 (1 mgr/kg) or vehicle was administered intraperitoneally for five consecutive days after ET-1-induced RGC loss. The functional extent of RGC loss injury was evaluated with pattern visual evoked potentials (VEP) and electroretinography. RGCs and retinal nerve fiber layer (RNFL) thickness were assessed in vivo using optical coherence tomography and ex vivo using Brn3a immunohistochemistry in flat-mounted retinas. ET-1 caused significant RGC loss and function loss one week after intravitreal injection. VEP showed preserved visual function after CYM-5442 administration compared to vehicle-treated animals (11.95 ± 0.86 µV vs 3.47 ± 1.20 µV, n = 12) (p < 0.05). RNFL was significantly thicker in the CYM treated-animals compared to the vehicle (93.62 ± 3.22 µm vs 77.72 ± 0.35 µm, n = 12) (p < 0.05). Furthermore, Brn3a immunohistochemistry validated this observation, showing significantly higher RGCs numbers in CYM treated rats than in the vehicle group (76,540 ± 303 vs 52,426 ± 1,932 cells/retina, n = 9) (p = 0.05). CYM-5442 administration was associated with significant retinal cleaved caspase-3 deactivation, indicating reduced apoptotic levels. The results of the present study further demonstrate the important role of S1P1 receptor agonists to lessen intravitreal ET-1 induced RGC loss.

Evaluation of visual function and retinal structure in adult amblyopes.

PURPOSE: To evaluate visual function and its relationship to structure in adult amblyopic subjects. METHODS: This observational, cross-sectional study included 24 adult amblyopes and 19 healthy subjects. The amblyopes were separated into three groups: anisometropic amblyopes (n = 15), strabismic amblyopes (n = 5), and strabismic amblyopes with anisometropia (n = 4). The relationships of the multifocal visual evoked potential (VEP) results with the clinical findings and psychophysical (Humphrey visual field) and structural (spectral domain optical coherence tomography) diagnostic test data were then investigated. RESULTS: Significant differences in the multifocal VEP amplitude responses (abnormal cluster defects), combining the interocular and monocular probability analysis, were observed between the anisometropic amblyopic (80%) and nonamblyopic eyes (13.3%) (p < 0.001), whereas in strabismic amblyopia, such defects were found in 100% of the amblyopic and nonamblyopic eyes. Delayed multifocal VEP interocular and monocular latencies were seen in 66.6 and 26.6% of the anisometropic amblyopic and nonamblyopic eyes, with no significant differences between eyes (p = 0.065). Likewise, latency delays were found in 40% of both strabismic amblyopic and nonamblyopic eyes. Multifocal VEP latency showed significant differences between anisometropic and strabismic amblyopic eyes (p = 0.036). Significant agreement was found between the Humphrey visual field and the multifocal VEP visual field defects in the central area of the visual field (p = 0.033). The average retinal nerve fiber layer thickness, foveal and macular thickness, and macular volume, as measured by spectral domain optical coherence tomography, did not show any significant differences between the amblyopic and nonamblyopic eyes and the control group. CONCLUSIONS: Multifocal VEP amplitudes and latencies were significantly affected in amblyopic eyes and, to a lesser extent, in nonamblyopic eyes. Multifocal VEP response latencies were more delayed in anisometropic eyes than in strabismic eyes, suggesting that anisometropic and strabismic amblyopia may represent different neural abnormalities.

Functional assessment of the visual pathway with multifocal visual evoked potentials, and their relationship with disability in patients with multiple sclerosis.

OBJECTIVE: To objectively evaluate the visual function, and the relationship between disability and optic nerve dysfunction, in patients with multiple sclerosis (MS) and optic neuritis (ON), using multifocal visual evoked potentials (mfVEP). METHODS: This observational, cross-sectional study assessed 28 consecutive patients with clinically definite MS, according to the McDonald criteria, and 19 age-matched healthy subjects. Disability was recorded using the Expanded Disability Status Scale (EDSS) score. The patients' mfVEP were compared to their clinical, psychophysical (Humphrey perimetry) and structural (optic coherence tomography (OCT)) diagnostic test data. RESULTS: We observed a significant agreement between mfVEP amplitude and Humphrey perimetry/OCT in MS-ON eyes, and between mfVEP amplitude and OCT in MS but non-ON eyes. We found significant differences in EDSS score between patients with abnormal and normal mfVEP amplitudes. Abnormal mfVEP amplitude defects (from interocular and monocular probability analysis) were found in 67.9% and 73.7% of the MS-ON and MS-non-ON group eyes, respectively. Delayed mfVEP latencies (interocular and monocular probability analysis) were seen in 70.3% and 73.7% of the MS-ON and MS-non-ON groups, respectively. CONCLUSIONS: We found a significant relationship between mfVEP amplitude and disease severity, as measured by EDSS score, that suggested there is a role for mfVEP amplitude as a functional biomarker of axonal loss in MS.

Obstructive sleep apnea-hypopnea syndrome (OSAHS) and glaucomatous optic neuropathy.

Obstructive sleep apnea-hypopnea syndrome (OSAHS) is becoming widely accepted as a risk factor for glaucoma. We discuss the proposed mechanism involved in the pathogenesis of glaucoma in OSAHS, and review the published data on the association between these two conditions, as well as papers regarding functional and structural tests related with glaucomatous damage. There is increasing evidence that the prevalence of glaucoma is higher in OSAHS patients, especially in those with severe disease with apnea-hypopnea index (AHI) >30, and also that sleep disorders may be more frequent in patients with glaucoma, especially in those with normal tension glaucoma (NTG). Several ophthalmic signs and symptoms have been associated with this condition. Raised intraocular pressure (IOP), possibly related to increased body mass index, thinning of retinal nerve fiber layer (RNFL), and alteration of visual field (VF) indices has been demonstrated in many studies, in patients with no history of glaucoma or evidence of glaucomatous changes in the ophthalmic examination. A correlation of AHI with RNFL and VF indices has been described in some studies. Finally, corneal thinning, suspicious glaucomatous disc changes and anomalies in electrophysiological tests such as multifocal visual evoked potential have been described in patients with OSAHS, even in patients with normal findings in the optic nerve and VF, suggesting subclinical optic nerve involvement not detectable in conventional ophthalmic examinations. The pathogenesis of optic nerve involvement has been related to vascular and mechanical factors. Vascular factors include recurrent hypoxia with increased vascular resistance, autonomic deregulation, oxidative stress and inflammation linked to hypoxia and subsequent reperfusion, decreased cerebral perfusion pressure and direct hypoxic damage to the optic nerve. Proposed mechanical factors include increased IOP at night related to supine position and obesity, raised intracranial pressure and elastic fiber depletion in the lamina cribosa and/or trabeculum. In conclusion, ophthalmic evaluation should be recommended in patients with severe OSAHS, and the presence of sleep disorders should be investigated in patients with glaucoma, especially in NTG patients and in those with progressive damage despite controlled IOP, as treatment with continuous positive airway pressure may contribute to stabilizing the progression of glaucomatous damage.

Electroretinographical and histological study of mouse retina after optic nerve section: a comparison between wild-type and retinal degeneration 1 mice.

BACKGROUND: Retinal ganglion cell death underlies the pathophysiology of neurodegenerative disorders such as glaucoma or optic nerve trauma. To assess the potential influence of photoreceptor degeneration on retinal ganglion cell survival, and to evaluate functionality, we took advantage of the optic nerve section mouse model. METHODS: Surviving retinal ganglion cells were double-stained by exposing both superior colliculi to fluorogold, and by applying dextran-tetramethylrhodamine to the injured optic nerve stump. To assess retinal function in wild-type animals, electroretinograms were recorded on the injured eyes and compared with the contralateral. Similar labelling experiments were carried out on retinal degeneration 1 mice. Surviving retinal ganglion cells were counted 21 days after axotomy and compared with wild-type mice. No functional experiments were performed on retinal degeneration 1 animals because they do not develop normal electroretinographical responses. RESULTS: A significant decrease in retinal ganglion cell density was observed 6 days after axotomy in the wild type. Functional studies revealed that, in scotopic conditions, axotomy induced a significant amplitude decrease in the positive scotopic threshold response component of the electroretinogram. Such decrease paralleled cell loss, suggesting it may be an appropriate technique to evaluate functionality. When comparing retinal ganglion cell densities in wild-type and retinal degeneration 1 mice, a significant greater survival was observed on the latter. CONCLUSIONS: After optic nerve section, electroretinographical recordings exhibited a progressive decrease in the amplitude of the positive scotopic threshold response wave, reflecting ganglion cell loss. Interestingly, rod degeneration seemed, at least initially, to protect from axotomy-driven damage.

Evaluation of multifocal visual evoked potentials in patients with Graves' orbitopathy and subclinical optic nerve involvement.

Dysthyroid optic neuropathy is the most serious, although infrequent (8-10 %) complication in Graves' orbitopathy (GO). It is known that early stages of compressive optic neuropathy may produce reversible visual field defects, suggesting axoplasmic stasis rather than ganglion cell death. This observational, cross-sectional, case-control study assessed 34 consecutive patients (65 eyes) with Graves' hyperthyroidism and longstanding GO and 31 age-matched control subjects. The patients' multifocal visual evoked potentials (mfVEP) were compared to their clinical and psychophysical (standard automated perimetry [SAP]) and structural (optic coherence tomography [OCT]) diagnostic test data. Abnormal cluster defects were found in 12.3 % and 3.1 % of eyes on the interocular and monocular amplitude analysis mfVEP probability plots, respectively. As well, mfVEP latencies delays were found in 13.8 and 20 % of eyes on the interocular and monocular analysis probability plots, respectively. Interestingly, 19 % of patients with GO had ocular hypertension, and a strong correlation between intraocular pressure measured at upgaze and mfVEP latency was found. MfVEP amplitudes and visual acuity were significantly related to each other (P < 0.05), but not with the latencies delays. However, relationships between the interocular or monocular mfVEP amplitudes and latencies analysis and SAP indices or OCT data were not statistically significant. One-third of our patients with GO showed changes in the mfVEP, indicating significant subclinical optic nerve dysfunction. In this sense, the mfVEP may be a useful diagnostic tool in the clinic for early diagnosis and monitoring of optic nerve function abnormalities in patients with GO.

Evaluation of the visual function in obstructive sleep apnea syndrome patients and normal-tension glaucoma by means of the multifocal visual evoked potentials.

BACKGROUND: This study was designed to objectively evaluate visual function and the causal relationship between sleep apnea and optic nerve dysfunction in patients with obstructive sleep apnea syndrome (OSAS) with or without diagnosis of normal-tension glaucoma (NTG) using multifocal visual evoked potentials (mfVEP). METHODS: This observational, cross-sectional study assessed 20 patients with recently diagnosed OSAS with or without NTG. Diagnosis of sleep apnea was based on overnight polysomnography (ApnoeScreen). All participants underwent a complete physical and ophthalmologic examination. MfVEP recordings obtained using VERIS software (Electro-Diagnostic Imaging, San Mateo, USA), SITA-standard 30-2 automated perimetry (Humphrey Visual Field Analyzer II) and optic coherence tomography (Topcon 3D OCT-1000) exams were performed to evaluate the changes. RESULTS: Abnormal mfVEP amplitudes defects (interocular and monocular probability analysis) were found in 40% of the eyes in the non-glaucoma group and in 90% of eyes of the NTG patients. As well, delayed mfVEP latencies (interocular and monocular probability analysis) were seen in 30 and 60% of the eyes of the non-glaucoma and NTG groups, respectively. The average RNFL (retinal nerve fiber layer) thickness was significantly reduced in the NTG eyes compared to the control database and the non-glaucoma eyes. On the Humphrey Visual Field total deviation analysis, all the NTG eyes showed significant clusters of abnormal points but none was detected in the non-glaucoma group eyes. However, the mfVEP amplitude and latency did not show any significant correlation with the standard perimetry and OCT variables, because the mfVEP technique was able to detect far more early visual defects in these patients. Systolic blood pressure, sleep efficiency, arousal index, mean and minimum arterial oxygen saturation (SaO(2)), time SaO(2) < 90%, oxyhemoglobin desaturation index, number of central and mixed apneas and apnea-hipopneas index were shown to be significantly correlated with mfVEP amplitude and latency. CONCLUSIONS: A significant incidence of subclinical optic nerve involvement, not detected with other structural and psychophysics diagnostic techniques was seen by means of the mfVEP. In this sense, the mfVEP may be a useful diagnostic tool in the clinic for early diagnosis and monitoring of optic nerve function abnormalities in patients with OSAS.

Prospective Evaluation of the First Mitomycin C Augmented Needle Revision in Patients With Failed Nonpenetrating Deep Sclerectomy.

PRECIS: At 6 months the procedure achieved a 33.89% drop in intraocular pressure (IOP), had an overall success rate of 57.15%, and did not change the best-corrected visual acuity. Achieving <8 mm Hg of IOP the day after the procedure may be a prognostic success indicator. PURPOSE: The purpose of this study was to evaluate the first mitomycin C (MMC)-augmented needle revision in patients with failed nonpenetrating deep sclerectomy (NPDS) and factors associated with its success. MATERIALS AND METHODS: This prospective, nonrandomized comparative trial included 21 consecutive patients (21 eyes) who underwent their first MMC needling revision of failed NPDS blebs. The success was defined as absolute if the IOP decreased >20% from the preoperative value without antiglaucoma treatment and as qualified if that level was achieved with antiglaucoma medications. Preoperative and postoperative factors were evaluated for an association with postoperative success using Kaplan-Meier analysis. RESULTS: A significant reduction in mean IOP from preoperative levels was evident at the end of the follow-up. The overall surgical success rate was 57.15%. On the basis of Kaplan-Meier survival analysis, we found that patients whose IOP on the following day of the procedure was <8 mm Hg had a higher success rate than those whose 1-day postoperative IOP was higher. These patients had a percentage of success of 100%, 84.6%, and 76.9% at 1-, 3-, and 6-month postoperative follow-up, respectively. CONCLUSION: The IOP level on the first postoperative day could be considered a prognostic indicator of success in needling revision performed in failed NPDS.

The Role of the Stromal Extracellular Matrix in the Development of Pterygium Pathology: An Update.

Pterygium is a benign fibrovascular lesion of the bulbar conjunctiva with frequent involvement of the corneal limbus. Its pathogenesis has been mainly attributed to sun exposure to ultraviolet-B radiation. Obtained evidence has shown that it is a complex and multifactorial process which involves multiple mechanisms such as oxidative stress, dysregulation of cell cycle checkpoints, induction of inflammatory mediators and growth factors, angiogenic stimulation, extracellular matrix (ECM) disorders, and, most likely, viruses and hereditary changes. In this review, we aim to collect all authors' experiences and our own, with respect to the study of fibroelastic ECM of pterygium. Collagen and elastin are intrinsic indicators of physiological and pathological states. Here, we focus on an in-depth analysis of collagen (types I and III), as well as the main constituents of elastic fibers (tropoelastin (TE), fibrillins (FBNs), and fibulins (FBLNs)) and the enzymes (lysyl oxidases (LOXs)) that carry out their assembly or crosslinking. All the studies established that changes in the fibroelastic ECM occur in pterygium, based on the following facts: An increase in the synthesis and deposition of an immature form of collagen type III, which showed the process of tissue remodeling. An increase in protein levels in most of the constituents necessary for the development of elastic fibers, except FBLN4, whose biological roles are critical in the binding of the enzyme LOX, as well as FBN1 for the development of stable elastin. There was gene overexpression of TE, FBN1, FBLN5, and LOXL1, while the expression of LOX and FBLN2 and -4 remained stable. In conclusion, collagen and elastin, as well as several constituents involved in elastic fiber assembly are overexpressed in human pterygium, thus, supporting the hypothesis that there is dysregulation in the synthesis and crosslinking of the fibroelastic component, constituting an important pathogenetic mechanism for the development of the disease.

Evaluation of functional integrity of the retinohypothalamic tract in advanced glaucoma using multifocal electroretinography and light-induced melatonin suppression.

The aim of the study was to investigate the survival of melanopsin-expressing retinal ganglion cells (mRGCs) and the functional integrity of the retinohypothalamic tract in patients with bilateral advanced glaucomatous optic neuropathy by measuring the neuroendocrine light response of the pineal gland. Nine patients with bilateral advanced primary open-angle glaucoma (glaucoma group) and nine normal control subjects (control group) were included in this pilot observational, prospective, case-control study. The best-corrected visual acuity logMAR, standard automated perimetry mean deviation, and the retinal nerve fiber layer thickness determined by optical coherence tomography and multifocal electroretinography were used to evaluate the changes. Melatonin was analyzed in the saliva by radioimmunoassay before and after exposure to bright light (600 lux) for 60 min at night. The advanced glaucoma group did not have any significant nocturnal melatonin suppression after exposure to bright light (14.28 ± 3.07 pg/ml pre-light melatonin concentration vs. 15.22 ± 3.56 pg/ml after light exposure; p = 0.798) unlike the marked melatonin suppression in the control group (22.43 ± 4.37 pg/ml pre-light melatonin concentration vs. 11.25 ± 1.89 pg/ml after light exposure; p < 0.002). Response density estimates by the scalar product amplitude measure for the interval 0-80 ms of the first-order kernel responses were similar in both groups, indicating that outer retinal function was significantly unchanged in the glaucoma group (5.95 ± 0.54 nV/dg^2) compared with the control group (6.20 ± 0.22 nV/dg^2) (p = 0.689). Our findings are consistent with the interpretation that the rhythmic secretion of melatonin was affected in advanced glaucoma, suggesting that attention should be paid to non-image-forming visual functions, such as control of circadian rhythm and the clinical impact in patients with glaucoma.

Kainic acid intraocular injections during the postnatal critical period induce plastic changes in the visual system.

Changes in the retino-collicular projection and in the number of optic nerve (ON) axons in adult rats were analyzed after partial loss of retinal ganglion cells (RGCs), induced by intravitreal injections of kainic acid (KA) on postnatal days 2-3 (P2-P3) or 10-12 (P10-P12). KA injected at P2-P3 decreased the volume of the adult contralateral superior colliculus (SC) and the density of the retino-collicular contralateral projection, but maintained the neonatal pattern in the ipsilateral projection from the un-injected eye. ON axon number was significantly increased in the un-injected eye but decreased in the KA-injected eye. Thus, restriction of the ipsilateral retino-collicular projection and RGC death in the un-injected eye are modified by KA at P2-P3, during the postnatal critical period, but not at P10-P12, after it is over. We suggest that, in the SC contralateral to the KA-injected eye, the disappearance of axon terminals belonging to RGC killed by KA would decrease competition between ipsilateral and contralateral terminals, thus contributing to maintaining the neonatal pattern in the ipsilateral retino-collicular projection. The reduction in RGC death in the un-injected eye could also be related to the disappearance of RGC terminals in the contralateral SC, which would have increased neurotrophic factor availability.

Elevated blood/lymphatic vessel ratio in pterygium and its relationship with vascular endothelial growth factor (VEGF) distribution.

INTRODUCTION: Pterygium is a conjunctival fibrovascular tissue growth on the cornea. The pathogenesis of pterygium involves several factors such as the presence of active angiogenic factors. Expansion of the lymphatic microvasculature has also been hypothesized. This study examines the activity of the angiogenic/lymphangiogenic factor VEGF and the expression of vascular and lymphatic endothelial proteins in pterygia and normal conjunctival tissues. MATERIAL AND METHODS: Primary grade 2 pterygium (n=20) and normal conjunctiva (n=20) biopsies were obtained during surgery after written informed consent. mRNA expression for CD31, podoplanin, and VEGF (isoforms VEGF-A and VEGF-165) were determined by qRT-PCR. Tissue samples were also processed for immunohistochemical techniques to examine the lymphatic and vascular endothelium (anti-D2-40, anti-CD31 respectively) and VEGF-A and VEGF-C levels and distribution. RESULTS: VEGF-A gene expression levels failed to differ between the healthy and pterygium tissues. However, expression of its more angiogenic isoform, VEGF-165, was significantly higher in the pterygia. Immunohistochemistry revealed the greater presence of VEGF-A, compared to VEGF-C, in pterygium than conjunctiva, both in blood vessels and extracellular matrix. In addition, pterygia showed higher expression levels of the endothelial junction protein CD31. Lymphatic marker D2-40 expression was slightly augmented in this pathological tissue. The ratio between blood and lymphatic vessel counts was 1.05 in the normal conjunctiva and 3-fold this value in pterygium. CONCLUSION: In pterygium, while both lymphangiogenesis and angiogenesis take place, the formation of new blood vessels is the most relevant event, correlating with the increased expression of vascular endothelial CD31 and an elevated blood/lymphatic vessel ratio. The presence of high levels of VEGF-A in both vessel networks and extracellular matrix in human pterygium tissue may have a major impact on angiogenesis in this pathological tissue.

Treating amblyopia in adults with prosthetic occluding contact lenses.

PURPOSE: To investigate the feasibility, effectiveness and acceptability of using prosthetic occluding contact lenses (OCLs) to treat moderate amblyopia in adults and of the role of the multifocal visual evoked potential (mfVEP) as a predictor of postamblyopic therapy. METHODS: A comparative, prospective, interventional, case series pilot study with amblyopic adults (mean age: 40 years, range 20-50 years) allocated into two intervention groups: eye patching and OCL. The primary outcome variable was logarithm of the minimum angle of resolution (logMAR) best-corrected visual acuity (BCVA), and secondary outcomes were mfVEP amplitude and latency and patients' health-related quality of life National Eye Institute Visual Function Questionnaire (NEI VFQ-25). RESULTS: Significant improvements in pre- to postamblyopic therapy BCVA were seen at 1.5 months in the OCL group [0.29 logMAR, 95% confidence interval (CI): 0.10-0.47 versus 0.11 logMAR, 95% CI: 0.02-0.19; p < 0.001] and eye patching group (0.29 logMAR, 95% CI: 0.17-0.40 versus 0.18 logMAR, 95% CI: 0.12-0.23; p < 0.01). Post-treatment BCVA was inversely related to age (R: 0.009, 95% CI: -0.02 to -0.001; p = 0.04) and the presence of strabismus (R: -0.3, 95% CI: -0.434 to -0.17; p = 0.001). No significant changes in the number and size of the abnormal mfVEP amplitude and latency defects were observed after occlusion. The NEI VFQ-25 composite score showed significant improvement in the OCL users at 12 months compared to eye patching. CONCLUSION: Significant vision improvement can be achieved, making occlusion with OCLs an effective and more acceptable therapy for adults with amblyopia.

Visante Anterior Segment Optical Coherence Tomography Analysis of Morphologic Changes in the Anterior Segment Structures after Deep Sclerotomy Versus Phaco-Deep Sclerotomy with Intraoperative Mitomycin-C and No Implant Use.

This article has been retracted.

Effect of diabetes mellitus on Corvis ST measurement process.

PURPOSE: Diabetes mellitus (DM) affects corneal biomechanical parameters. We compared analyses using ORA (Ocular response analyser) and Corvis ST to determine the influence of disease duration, hyperglycaemia and haemoglobin A1c (HbA1c) levels on these parameters. METHODS: This observational, cross-sectional, observer-masked study assessed one eye of 94 consecutive DM patients and 41 healthy subjects. Two DM groups were analysed: the uncontrolled DM group (n = 54) (HbA1c ≥ 7%) and the controlled DM group (n = 40) (HbA1c < 7%). Central corneal thickness (CCT) was measured by ultrasonic pachymetry and intraocular pressure (IOP) by Goldmann applanation tonometry. ORA and Corvis ST analyses were performed to evaluate the changes. RESULTS: Most of the Corvis ST parameters [Deformation amplitude (DA), A1 and A2 times, A1 velocity] in the uncontrolled DM group eyes were found to be significantly different to controls and controlled DM group eyes (p = 0.005, p = 0.001, p < 0.0001, p = 0.002, respectively). DA on the Corvis ST was correlated with blood glucose concentration (p = 0.004) and HbA1c percentage (p = 0.002). ORA corneal hysteresis was significantly lower in diabetic patients with elevated HbA1c than in control subjects (p = 0.001) and was affected by disease duration (p = 0.037), whereas the corneal resistance factor remained unaltered. CONCLUSIONS: A poor glucose control in DM affects corneal biomechanics measured by ORA and Corvis ST, which may cause high IOP measurements independent of CCT. The measurement of the corneal biomechanics should be taken into consideration in the clinical practice.

Elastin development-associated extracellular matrix constituents of subepithelial connective tissue in human pterygium.

PURPOSE: We evaluated the expression of several extracellular matrix constituents implicated in the synthesis and reticulation of elastin in human pterygium, according to age and sex of the patients. METHODS: Pterygia and normal conjunctiva samples were divided into groups according to age (<50/≥50 years) and sex. Tissue was subjected to immunohistochemical staining with anti-lysyl oxidase (LOX), lyxyl oxidase-like 1 (LOXL-1), fibulin (FBLN)-5 and FBLN4, and fibrillin-1 (FBN1) antibodies. Specific primers for the same constituents were used in a quantitative real-time PCR (qRT-PCR) analysis to determine gene expression. RESULTS: The LOXL-1 (P = 0.0002), FBLN5 (P = 0.0035), and FBN1 (P < 0.0001) mRNAs were significantly higher in pterygium than conjunctiva. No differences were found for LOX and FBLN4 mRNA. The expression of LOXL-1 was not affected by age or sex; however, pterygium from men and patients over 50 years old exhibited significantly higher FBLN5/FBN1 expression than did controls. The LOX gene expression was higher in the pathologic samples from the over 50-year-olds compared to the conjunctiva (P = 0.0396) and in men's versus women's pterygium (P = 0.0173). In general, the levels of LOX, LOXL-1, and FBLN5 decreased with age in healthy samples, while the pathology seemed to have increased expression of the three proteins, and even more so in older patients. The FBLN4 and FBN1 immunostaining was slight in all samples, displaying no differences between groups. CONCLUSIONS: Several extracellular matrix constituents, LOXs, FBN1, and FBLN5, implicated in the development of elastin, are overexpressed in the subepithelial connective tissue extracellular matrix of human pterygium, supporting our hypothesis that elastic synthesis and reticulation is dysregulated in this type of pathology.

Visante anterior segment optical coherence tomography analysis of morphologic changes after deep sclerectomy with intraoperative mitomycin-C and no implant use.

PURPOSE: To assess long-term intrascleral space maintenance after nonpenetrating deep sclerectomy (NPDS) without implant placement and with application of intraoperative mitomycin-C, using Visante anterior segment optical coherence tomography (AS-OCT). PATIENTS AND METHODS: This cross-sectional, observational, case series study examined 47 eyes from 47 consecutive patients who had undergone NPDS 58.34±23.77 months earlier. All participants underwent a complete ophthalmologic examination. The presence of intrascleral space and its maximum anteroposterior and transverse lengths, maximum height, and volume were evaluated. The thickness of the trabeculo-Descemet membrane, presence and type of any subconjunctival filtering bleb, as well as scleral and suprachoroidal hyporeflectivity were analyzed. Relationships between intraocular pressure (IOP) levels and AS-OCT parameters were established. RESULTS: AS-OCT examinations revealed an open intrascleral space in all cases. The IOP was negatively correlated with the maximum anteroposterior length, maximum height, and volume of intrascleral space. Significant differences in IOP were found between eyes with low-reflective blebs and eyes with other subconjunctival bleb types. The overall surgical success rate was 89.4%. CONCLUSIONS: NPDS without implant placement and with intraoperative mitomycin C application seems to be an effective and well-tolerated method to reduce IOP with long-term effectiveness, casting doubt on the mandatory use of intrascleral implants in nonpenetrating glaucoma surgery.

Evaluation of visual structural and functional factors that predict the development of multiple sclerosis in clinically isolated syndrome patients.

PURPOSE: To evaluate visual pathway structure and function in patients with clinical isolated syndrome (CIS) by using spectral-domain optical coherence tomography (OCT) and multifocal visual-evoked potentials (mfVEP), predicting CIS conversion to clinically definite multiple sclerosis (MS). METHODS: This observational, longitudinal study assessed the eyes with no previous history of optic neuritis of 29 consecutive patients with CIS according to the McDonald criteria. The relationships of the mfVEP results with the clinical findings, and psychophysical (Humphrey perimetry) and structural (OCT) diagnostic test data were investigated. RESULTS: The mfVEP amplitude responses (interocular and monocular probability analysis) showed abnormal cluster visual field defects in 48.3% of the CIS eyes, whereas mfVEP latency analysis showed significant delays in 20.7%. The OCT average retinal nerve fiber layer thickness (RNFLT) was significantly reduced compared with the control group (P = 0.02). Significant differences between CIS eyes with abnormal and normal mfVEP latencies were found for the OCT RNFLT (P < 0.001) with a longer latency being linked to more severe axonal damage. Using multivariate logistic regression analysis, OCT average RNFLT was found to be an independent predictor of clinically definitive MS diagnosis at 12 months. CONCLUSIONS: The combined use of OCT and mfVEP is helpful to detect significant subclinical visual pathway abnormalities and axonal loss in CIS patients. Retinal axonal loss measured by OCT is an important prognostic factor of conversion to MS in patients with CIS in absence of symptomatic optic neuritis.