Neuroprotection in Glaucoma: Old and New Promising Treatments.

Glaucoma is a major global cause of blindness, but the molecular mechanisms responsible for the neurodegenerative damage are not clear. Undoubtedly, the high intraocular pressure (IOP) and the secondary ischemic and mechanical damage of the optic nerve have a crucial role in retinal ganglion cell (RGC) death. Several studies specifically analyzed the events that lead to nerve fiber layer thinning, showing the importance of both intra- and extracellular factors. In parallel, many neuroprotective substances have been tested for their efficacy and safety in hindering the negative effects that lead to RGC death. New formulations of these compounds, also suitable for chronic oral administration, are likely to be used in clinical practice in the future along with conventional therapies, in order to control the progression of the visual impairment due to primary open-angle glaucoma (POAG). This review illustrates some of these old and new promising agents for the adjuvant treatment of POAG, with particular emphasis on forskolin and melatonin.

Relationship between Corneal Temperature and Intraocular Pressure in Healthy Individuals: A Clinical Thermographic Analysis.

Purpose. To study the geographical distribution of corneal temperature (CT) and its influence on the intraocular pressure (IOP) of healthy human volunteers. Materials and Methods. Fifteen subjects (7 M, 8 F), 33.8 ± 17.4 years old, were enrolled in this pilot, cross-sectional study. Measurements of CT were taken after one hour with closed eyelids (CET) or closed eyelids with a cooling mask (cm-CET) and compared to baseline. Results. If compared to baseline, after CET, average CT significantly increased by 0.56°C in the RE and by 0.48°C in the LE (p < 0.001) and IOP concomitantly significantly increased by 1.13 mmHg and 1.46 mmHg, respectively, in each eye (p < 0.001). After cm-CET, average CT significantly decreased by 0.11°C and 0.20°C, respectively, in the RE and LE (RE p = 0.04; LE p = 0.024), followed by a significant IOP decrease of 2.19 mmHg and 1.54 mmHg, respectively, in each eye (RE p < 0.001; LE p = 0.0019). Conclusion. Significant variations of CT occurred after CET and cm-CET and were directly correlated with significant differences of IOP. It can be speculated that both oxidative stress and sympathetic nerve fiber stimulation by temperature oscillations may affect the regulation of AH vortex flow and turnover, thus influencing IOP values.

Oral Administration of Forskolin, Homotaurine, Carnosine, and Folic Acid in Patients with Primary Open Angle Glaucoma: Changes in Intraocular Pressure, Pattern Electroretinogram Amplitude, and Foveal Sensitivity.

PURPOSE: To evaluate the effects of a food supplement containing forskolin, homotaurine, carnosine, folic acid, vitamins B1, B2, B6, and magnesium in patients with primary open angle glaucoma (POAG) already in treatment and compensated by intraocular pressure (IOP)-lowering drugs, during a period of 12 months. METHODS: Twenty-two patients (44 eyes) with POAG, with their IOP compensated by topical drugs, were enrolled and randomly assigned to the food supplement or control treatment group. The additional food supplement treatment consisted of 2 tablets per day (1 in the morning, 1 in the evening) given for 1 year of a balanced association of homotaurine, Coleus forskohlii root extract, L-carnosine, folic acid, vitamins B1, B2, B6, and magnesium. Pattern Electroretinogram (PERG) amplitude, foveal sensitivity obtained with the visual field analyzer frequency doubling technology, and IOP were detected at enrollment (T0), 3 months (T1), 6 months (T2), 9 months (T3), and 12 months (T4). RESULTS: We observed in treated patients a significant further decrease of IOP and an improvement of PERG amplitude at 6, 9, and 12 months, and foveal sensitivity at 12 months. All values remained substantially stable in control patients. CONCLUSIONS: The results of the present pilot study indicate that the components of the food supplement reach the eye in a detectable manner, as evidenced by the effects on the IOP. Moreover, they suggest a short-term neuroactive effect, as indicated by the improvement of PERG amplitude and foveal sensitivity in treated, but not in control patients.

Ocular Inflammation: Can It Be a Sign of Activity of Weber-Christian Disease? A Case Report and Review of Literature.

PURPOSE: To present a case of Weber-Christian disease with symptomatic ocular involvment. Weber-Christian disease is a relapsing febrile nodular nonsuppurative panniculitis. It is characterized by malaise and fever accompanied by subcutaneous inflammatory nodules on the trunk and extremities. It can affect several organs, but ocular signs have been infrequently described in literature. METHODS: A 20-year-old woman with Weber-Christian disease presented with severe bilateral ocular inflammation. A complete ophthalmologic examination was performed. RESULTS: Visual acuity was 20/100 in both eyes and slit-lamp examination showed bilateral iridocyclitis. Bilateral cortico-nuclear cataract did not allow funduscopy and she underwent cataract extraction. Retinal vasculitis was detected. CONCLUSIONS: Patients with Weber-Christian disease can develop severe ocular inflammation. A complete ophthalmolgic examination should be done in these patients, especially when ocular involvement is the main sign of the disease. A further understanding of the severity of ocular inflammation proved fundamental in the management of the disease.

Macular Pigment Optical Density and Measures of Macular Function: Test-Retest Variability, Cross-Sectional Correlations, and Findings from the Zeaxanthin Pilot Study of Response to Supplementation (ZEASTRESS-Pilot).

We report on the short-term test-retest baseline variability in macular function tests in ZEASTRESS-Pilot participants (n = 18), on their cross-sectional correlation with macular pigment optical density (MPOD), and on the effects of four months (FUV4) of 20 mg/day zeaxanthin (ZX), followed by a four-month washout (FUV8; n = 24, age 50-81 years old). Outcomes included: MPOD at 0.5 and 2.0 deg eccentricity (MPOD-0.5 and -2.0); contrast sensitivity (CS); pattern-reversal electroretinogram (PERG) amplitude; dark-adapted 650 nm foveal cone sensitivity (DA650-FCS); and 500 mn parafoveal rod sensitivity (DA500-PFRS). All measures of macular function showed close test-retest correlation (Pearson's r range: 0.744-0.946) and low coefficients of variation (CV range: 1.13%-4.00%). MPOD correlated in a complex fashion with macular function. Following supplementation, MPOD-0.5 and MPOD-2.0 increased at both FUV4 and FUV8 (p ≤ 0.0001 for all measures). Continued, delayed MPOD increase and a small, but significant (p = 0.012), CS increase was seen at FUV8 only in females. PERGs increased significantly at FUV4 (p = 0.0006), followed by a partial decline at FUV8. In conclusion, following ZX supplementation, MPOD increased significantly. There was no effect on DA-650 FCS or DA-500 PFRS. Both CS and PERG amplitudes increased following supplementation, but the effect varied between males and females. Additional studies appear warranted to confirm and characterize further these inter-gender differences.

Reduction in retinal nerve fiber layer thickness in tuberous sclerosis complex.

PURPOSE: The aim of our study was to non-invasively investigate central nervous system axonal integrity in patients with tuberous sclerosis complex (TSC). Diffuse microstructural white matter abnormalities reflecting axonal disorganization, reduced/altered myelination, or gliosis have been described in individuals with TSC. Optical coherence tomography (OCT) is a fast, easy-to-perform, non-invasive, and cost-efficient method to assess retinal morphology in vivo and to measure the thickness of the retinal nerve fiber layer (RNFL). METHODS: In order to assess central nervous system axonal integrity, eight subjects with TSC have been investigated by OCT to evaluate RNFL and they have been compared with matched healthy controls. RESULTS: When comparing mean overall RNFL thicknesses of the TSC group with those of the control group, the TSC group presented with significantly lower RNFL values, compared to the control group, in the temporal quadrant (62.5 ± 6.9 vs. 76.9 ± 5.4; t = 14.438; p < 0.0001). CONCLUSIONS: Since a reduced RNFL thickness might be seen as an indicator of chronic axonal degeneration or lack of appropriate neuronal development, our results support the presence of axonal alterations in TSC and also that white matter disorganization could be much more diffuse than originally thought. Since axonal alterations directly derive from mammalian target of rapamycin (mTOR) overactivation, which occurs early during fetus development, the RNFL thinning we observed could represent one of the facets of such early neurodevelopmental abnormalities.

Reduction in retinal nerve fiber layer thickness in young adults with autism spectrum disorders.

Recent years have seen an increase in the use of retinal nerve fiber layer (RNFL) evaluation as an easy-to-use, reproducible, proxy-measure of brain structural abnormalities. Here, we evaluated RNFL thickness in a group of subjects with high functioning autism (HFA) or with Asperger Syndrome (AS) to its potential as a tool to study autism pathophysiology. All subjects underwent high-resolution spectral domain optical coherence tomography to evaluate RNFL thickness. HFA subjects presented with reduced global RNFL thickness compared both to AS subjects and controls. AS subjects showed a reduced nasal quadrant RNFL thickness compared to controls. Verbal-IQ/performance-IQ discrepancy correlated with RNFL thickness. Our data suggest that RNFL evaluation could help in the development of biological markers of autism pathophysiology.

Intracoital subfoveal hemorrhage after tadalafil (cialis) premedication: a case report.

PURPOSE: The purpose of this study is to report the first case, to our knowledge, of intracoital subfoveal hemorrhage occurring 1 hour after tadalafil premedication in a patient with previously undiagnosed retinal angiomatous proliferation and erectile dysfunction. METHODS: This is an interventional case report. The patient underwent Snellen vision acuity measurement, anterior and posterior segment biomicroscopy, and indirect ophthalmoscopy. Optical coherence tomography, fluorescein angiography, and indocyanine green angiography were also performed as needed. Recombinant tissue plasminogen activator 100 µg/0.1 mL and 0.3 mL pure SF6 gas were injected in the vitreous on presentation. Four days later, the patient received 1.25 mg/0.1 mL of intravitreal bevacizumab. RESULTS: One day after recombinant tissue plasminogen activator and gas injection, visual acuity rose to 20/60-2. A week later, visual acuity was unchanged, and the subretinal hemorrhage displaced from the foveola. Optical coherence tomography showed a marked regression of submacular thickening. CONCLUSION: Despite strict time correlation, the submacular hemorrhage cannot be unequivocally attributed to tadalafil assumption because many other risk factors are to be considered: the Valsalva maneuver above all. Nonetheless, a suspicion should be raised, at least as a cofactor, given the drug mechanism of action and the report of vascular abnormalities bleeding in the literature, including cerebral arterovenous malformation and epistaxis. Caution should be exercised in the prescription of phosphodiesterase type 5 inhibitors to patients with known vascular abnormalities including retinal and choroidal abnormalities: retinal angiomatous proliferation, classic and occult neovascularization of any origin, and also, possibly, hemangioma.

Combined pars plana vitrectomy and artificial iris diaphragm implant after globe rupture.

BACKGROUND: Retinal detachment (RD) associated with aniridia due to globe rupture (GR) is an uncommon condition with a severe prognosis. Surgical technique must address anterior and posterior segment issues secondary to the altered compartmentalization and increased risk for corneal toxicity. The purpose of this paper is to report a series of GR patients undergoing combined pars plana vitrectomy (PPV) and artificial iris diaphragm (AID) implant for the repair of RD associated to aniridia. METHODS: The authors retrospectively reviewed 12 consecutive patients operated on by a single surgeon. Surgery consisted of a standard three-port PPV with extensive bimanual dissection of vitreous base and ciliary body membrane and combined AID implant. Office visits included Snellen visual acuity (VA), intraocular pressure measurement, biomicroscopy and indirect ophthalmoscopy. AID prosthesis included aniridic IOLs, Heimann's PMMA and silicone diaphragm. RESULTS: Mean age was 53 years and mean follow-up was 19 months. At the end of follow-up, seven patients gained more than two lines (58.3%), two lost their vision (16.6%) and three were unchanged (25%). Seven patients (58.3%) had a VA better than 20/400 and one (8%) 20/40 vision. Eight patients (66.6%) retained a clear cornea, two (16.6%) had minimal corneal oedema and two (16.6%) corneal decompensation. Implanted prosthesis included two silicone diaphragms, four PMMA diaphragms and six aniridic IOLs. After an average 1.6 operations, the retina was completely attached in six patients (50%), partially attached in four (33.3%) and detached in two (16.6%). CONCLUSION: RD associated to GR carries a guarded prognosis both due to RD complexity and hypotony. The combined repair of RD and aniridia after GR offers the advantage of addressing all issues at one time allowing correct eye compartmentalization and better tamponade effect. Successful anatomical and functional results can be achieved although multiple surgeries are often needed.