Effect of Femtosecond Laser Cataract Surgery on Peripapillary Retinal Nerve Fiber Layer Thickness.

PRCIS: Femtosecond laser-assisted cataract surgery (FLACS) may cause thinning of the peripapillary retinal nerve fiber layer (pRNFL) in healthy eyes. PURPOSE: This prospective cohort study aimed to compare changes of pRNFL after FLACS using a liquid patient interface and conventional phacoemulsification cataract surgery (CPCS). PATIENTS AND METHODS: Included were 261 eyes (261 patients) with age-related cataracts and no ocular diseases scheduled either for FLACS (222 eyes) or CPCS (39 eyes). FLACS was performed using a Ziemer LDV Z8 laser. Average and quadrant pRNFL thickness was measured using optical coherence tomography before surgery and at 1, 3, and 6 months postoperatively. Postoperative changes in pRNFL thickness were compared within and between groups. RESULTS: Mean quadrant and average pRNFL thicknesses significantly increased after both surgeries (P<0.001). However, pRNFL thinning occurred after FLACS and CPCS (17% vs. 5.1%, respectively, P>0.05). FLACS eyes showed a significant and stable decrease of average pRNFL thickness (P=0.057) and a gradual decrease in pRNFL thickness of all quadrants (P≤0.018). CPCS eyes showed an initial increase of pRNFL thickness, followed by a decrease only in the nasal quadrant and average pRNFL. Preoperative pRNFL thickness was associated with thinning of the temporal quadrant (P=0.04). CONCLUSIONS: Both FLACS and CPCS demonstrated pRNFL thinning in some healthy eyes. Although the higher rate of pRNFL thinning after FLACS compared with CPCS lacked statistical significance, a consistent decrease in pRNFL thickness occurred in all quadrants and average pRNFL of FLACS eyes, suggesting that FLACS may lead to pRNFL thinning. Eyes with thinner preoperative pRNFL may be prone to temporal quadrant thinning after FLACS.

[CHILDHOOD GLAUCOMA].

INTRODUCTION: "Childhood glaucoma" is a heterogenic group of diseases, characterized by elevated intraocular pressure (IOP) associated with optic-disc damage and other ocular comorbidities. Diagnosis requires two or more of the following: elevated IOP, optic nerve damage, enlarged cornea or Descemet's membrane ruptures, enlarged eye, high myopia and visual field defects. Childhood glaucoma is classified as primary if it occurs as an isolated ocular disease, and secondary, when the disease occurs along with other ocular anomalies or systemic diseases such as Neurofibromatosis and Sturge-Weber, or with acquired conditions such as uveitis complications, ocular trauma, cataract surgery, as well as from systemic and ocular steroid use. The clinical manifestations of childhood glaucoma depend on the age of presentation. In newborns, an enlarged eye with an enlarged cloudy cornea can be found, while infants present with an enlarged eye and signs of tearing, blinking and glare. Older children are usually asymptomatic and the disease is discovered incidentally on eye examination for other ocular problems. Treatment of childhood glaucoma is complicated and demanding. Most types of pediatric glaucoma require surgery in order control IOP, while medical treatment has a supportive role. Different types of glaucoma surgery are indicated for different types of pediatric glaucoma. Regular lifelong monitoring, including IOP control and treatment for the prevention of amblyopia is necessary to obtain and maintain good vision.

Ex-PRESS Miniature Glaucoma Shunt Versus Ahmed Glaucoma Valve in the Surgical Treatment of Glaucoma in Pseudophakic Patients.

PURPOSE: The aim of this study was to compare the 3-year outcome of Ex-PRESS miniature glaucoma shunt versus Ahmed glaucoma valve in pseudophakic patients. PATIENTS AND METHODS: We retrospectively reviewed the records of patients with a history of clear corneal phacoemulsification alone, or failed trabeculectomy following phacoemulsification, who subsequently underwent Ahmed glaucoma valve (AGV) implantation or Ex-PRESS shunt surgery. The main outcome measure, surgical success, was defined as an intraocular pressure between 5 and 21 mm Hg and a 20% intraocular pressure reduction from baseline (with/without glaucoma medications) without glaucoma reoperation. RESULTS: In total, 92 patients (92 eyes) were included (43 AGV, 49 Ex-PRESS). Overall success at 3 years was 92.7% for AGV and 66.1% for Ex-PRESS (P=0.006). AGV had a higher success rate in patients with prior phacoemulsification and failed trabeculectomy (96% AGV vs. 64.1% Ex-PRESS; P=0.023). There was no difference in success rate for patients with only previous phacoemulsification (87.5% AGV vs. 69.4% Ex-PRESS; P=0.205). Glaucoma reoperation rates were 4.6% and 30.6% in the AGV and Ex-PRESS group, respectively (P=0.001). Both procedures had similar complication rates. CONCLUSIONS: AGV compared with Ex-PRESS shunt, had a higher success rate for secondary surgeries but not primary surgeries, in patients with prior clear corneal phacoemulsification. The AGV surgery also had a lower overall glaucoma reoperation rate.

[CANNABIS AND GLAUCOMA: AN ANCIENT LEGEND OR A NOVEL THERAPEUTIC HORIZON?].

Glaucoma causes damage to the optic nerve and compromises the visual field. The main risk factor of the disease is the level of the intra-ocular pressure. Therapeutic options include medical and surgical treatment, aimed to lower the intra-ocular pressure. Consumption of the cannabis plant (Cannabis Satival has been known since ancient times. It can be consumed orally, topically, intra-venous or by inhalation. The main active ingredient of cannabis is THC (Tetra-Hydro-Cannabinol). One of THC's reported effects is the reduction of intra-ocular pressure. Several studies have demonstrated temporary intra-ocular pressure decrease in both healthy subjects and glaucoma patients following topical application or systemic consumption. The effect was a short term one. It was followed by the development of resistance to the drug after prolonged intake and it was also accompanied by topical and systemic side effects. Cannabis may be considered as a therapeutic option in glaucoma. Its limited effect, development of resistance, acquired side effects and the accompanying psycho-active influence limit its advantage and cause its efficacy to be dubious. Therefore, cannabis treatment for glaucoma currently seems impractical and is not recommended by either the Israeli or the American glaucoma societies.

Retinal nerve fibre layer thickness measurements by optical coherence tomography in patients with sleep apnoea syndrome.

BACKGROUND: The study aims to investigate whether retinal nerve fibre layer (RNFL) abnormalities can be detected in patients with obstructive sleep apnoea/hypopnoea syndrome with normally appearing optic disc. DESIGN: This is an observational case-control study. PARTICIPANTS: One hundred and eight consecutive patients with moderate or severe obstructive sleep apnoea/hypopnoea syndrome (OSAHS) as determined by overnight polysomnography and normal looking discs and 108 age-matched healthy controls were included in the study. METHODS: All patients underwent RNFL examinations by optical coherence tomography using fast retinal nerve fibre layer thickness scan. MAIN OUTCOME MEASURES: The main outcome measure was RNFL thickness. RESULTS: Multivariate regression analysis results showed that the RNFL was thinner for a patient with OSAHS than that of a normal control in the average by 4.20 µm (P < 0.003), in the superior quadrant by 4.83 µm (P = 0.028) and in the inferior quadrant by 5.19 µm (P = 0.016). RNFL thickness did not correlate with the severity of the disease. CONCLUSIONS: RNFL thinning was detected in normal-looking discs of patients with advanced OSAHS, but the extent of this thinning did not correlate with the severity of the disease. Longitudinal follow-up is needed to clarify whether RNFL thinning in OSAHS patients with normal clinically appearing optic nerves will eventually lead to glaucoma.

Sustained elevation of intraocular pressure after intravitreal injections of bevacizumab in eyes with neovascular age-related macular degeneration.

BACKGROUND: The use of intravitreal anti-VEGF agents in general, and of bevacizumab (Avastin) in particular, has become the common first-line treatment of neovascular age-related macular degeneration (AMD). Several reports addressed the possible elevation of intraocular pressure (IOP) following intravitreal injection of anti-VEGF. The aim of this study was to determine the prevalence of sustained IOP elevation following intravitreal bevacizumab injections for neovascular AMD and identify possible risk factors for the development of increased IOP. METHODS: This retrospective cohort study included 174 consecutive patients (201 eyes) receiving intravitreal bevacizumab (1.25 mg/0.05 ml) as treatment for neovascular AMD. The records of the study patients were reviewed for age, gender, history of glaucoma, phakic status, IOP levels, length of follow-up, total number of injections, intervals between injections, and IOP management in eyes that exhibited IOP elevation. Sustained IOP elevation was defined as IOP ≥22 mmHg and a change from baseline of ≥6 mmHg recorded on at least two consecutive visits and lasting ≥30 days. Risk factors for an IOP increase were identified from the association between the studied variables and IOP elevations. RESULTS: Sustained IOP elevation was found in 22 of 201 eyes (11%). The increased IOP was controlled with topical medications in all eyes. Among the variables studied, only male gender [OR = 3.1, 95% CI (1.1, 8.5) p = 0.029] and length of interval between injections <8 weeks [OR = 3.0, 95%CI (1.1, 7.9), p = 0.028] emerged as risk factors for IOP elevation in a multivariable model. The prevalence of IOP elevation was significantly higher when the interval between injections was <8 weeks than ≥8 weeks (17.6 and 6%, respectively, p = 0.009). Pre-existing glaucoma was not associated with IOP elevation (p = 0.9). CONCLUSIONS: Sustained IOP elevations can occur in normotensive eyes undergoing intravitreal bevacizumab treatment for neovascular AMD. This phenomenon was related to shorter intervals between injections, with 8 weeks being taken as the cut-off point. AMD eyes that receive intravitreal bevacizumab injections need to be monitored for IOP changes, especially those in which the intervals between injections are <8 weeks.

Origin-specific epigenetic program correlates with vascular bed-specific differences in Rgs5 expression.

Cells from multiple origins contribute to vascular smooth muscle cell (VSMC) development. Phenotypic heterogeneity of VSMCs is associated with their point of developmental origin; however, the mechanisms driving such differences are unknown. We here examined the mechanisms controlling vascular bed-specific differences in Rgs5 expression during development. Rgs5 levels were similar across different regions of the vasculature in neonatal animals but were >15-fold higher in descending aortas compared with carotid arteries of adult mice. Thus, vessel bed-specific changes in regulation of Rgs5 expression occurred during vessel maturation. Examination of adult Rgs5-LacZ reporter mice revealed lower Rgs5 expression in VSMCs originating from the third (carotid artery) branchial arch compared with those originating in the fourth and sixth (aortic B segment, right subclavian, and ductus arteriosus) branchial arches. Indeed, a mosaic Rgs5 expression pattern, with discreet LacZ boundaries between VSMCs derived from different developmental origins, was observed. Furthermore, Rgs5-LacZ expression was correlated with the site of VSMC origin (splanchic mesoderm ≈ local mesenchyme > somites > proepicardium > mesothelium). Surprisingly, Rgs5 reporter activity in cultured carotid artery- and descending aorta-derived cells did not recapitulate the differences observed in vivo. Consistent with a developmental origin-specific epigenetic mechanism driving the observed expression differences in vivo, the Rgs5 promoter showed increased methylation on CpG dinucleotides in carotid arteries compared with that in descending aortas in adult but not in neonatal mice. In vitro methylation of the Rgs5 promoter confirmed that its activity is sensitive to transcriptional down-regulation by CpG methylation. These data suggest that an origin-dependent epigenetic program regulates vascular bed- and maturation state-dependent regulation of VSMC-specific gene transcription.

MMP expression in leaking filtering blebs and tears after glaucoma filtering surgery.

OBJECTIVE: Glaucoma filtering surgery may be compromised by cystic blebs which develop more frequently when anti-metabolites are used to arrest wound healing. Matrix metalloproteinases (MMPs) and the naturally occurring tissue inhibitors of metalloproteinases (TIMPs) are essential in connective tissue remodeling and wound healing. This study aimed to determine whether filtering blebs display increased expression of MMP-2, MMP-9, TIMP-1 and TIMP-2, and whether it is reflected in tear fluid. METHODS: Tissue samples from leaking blebs (n = 5) and control conjunctiva (n = 5) were evaluated by immunohistochemistry for MMP-2, MMP-9, TIMP-1 and TIMP-2. Tear fluid was collected from 12 patients (12 eyes) with cystic blebs and ten patients (ten eyes) with flat blebs following trabeculectomy with Mitomycin C applied and 16 controls. MMP levels were evaluated by zymography and TIMP levels by Western blot analysis. RESULTS: Conjunctival tissue was obtained from five eyes with cystic leaking blebs and five control eyes undergoing cataract surgery. More extensive MMP-2 and MMP-9 expression was found in the epithelial and stromal layers of blebs than in control conjunctiva. TIMP-1and TIMP-2 were expressed in all layers of the blebs, but only in the epithelium of control conjunctiva. MMP-2 and proMMP-2 activity in tears from eyes with flat blebs was significantly higher than that of controls, while activity in tears of eyes with cystic blebs was significantly higher than in those with flat blebs. There was no difference in MMP-9 activity between tears of control and post-filtering surgery eyes. CONCLUSIONS: Increased MMPs and TIMPs expression is associated with the formation of filtering blebs, suggesting involvement of MMPs in bleb remodeling. MMP-2 and ProMMP-2 levels in tear fluid may be markers for bleb configuration.

The PI3K/Akt/mTOR pathway mediates retinal progenitor cell survival under hypoxic and superoxide stress.

Oxygen (O2) tension has emerged as a major regulator of stem cell (SC) biology. Low O2 concentrations that are toxic to mature cells can confer advantage to stem and early progenitors, while superoxide stress remains a constant threat in aerobic biology and may be partially avoided through sequestration of SCs in the relatively hypoxic stem or regenerative niche. Using primary retina-derived retinal progenitor cells (RPCs) and the R28 progenitor cell line in vitro, we show that RPCs are sensitive to hydrogen peroxide (H2O2) induced damage and resistant to moderate levels of low oxygen stress (1% O2). Under hypoxic conditions, multipotent RPCs upregulate Epo receptors, and Epo, along with insulin, protects against both superoxide- and severe hypoxia- (0.25% O2) induced apoptosis through activation of the canonical PI3K/Akt/mTOR pathway. This survival advantage is sensitive to inhibitors of PI3K and mTOR. We further demonstrate phosphorylation of the p70S6 ribosomal kinase, a downstream mediator of PI3K/Akt/mTOR and translational activator. Overall, these data confirm that RPCs are sensitive to superoxide stress and resistant to hypoxia and that this resistance is mediated in part by Epo. They further suggest that manipulation of RPCs ex vivo prior to ocular delivery, or the in vivo delivery of exogenous survival factors at the time of cell implantation, could enhance the success of regenerative therapies aimed to restore sight.

The involvement of matrix metalloproteinases 2 and 9 in rat retinal ischemia.

BACKGROUND: The involvement of matrix metalloproteinases (MMPs) in ischemic tissue damage and remodeling has been reported by many investigators. Our study was designed to investigate the involvement of MMPs and of tissue inhibitors of metalloproteinases (TIMPs) in rat retinal ischemic injury, the effect of nitric oxide synthase (NOS) inhibitors on MMPs' activity in this model and whether minocycline (an MMP inhibitor) is protective in retinal ischemia. METHODS: Ninety-four rats were used in the study. Ischemia was induced by 90 min elevation of intraocular pressure. MMPs' activities and the effect of NOS inhibitors [aminoguanidine (AG) or N-nitro-L-arginine (NNA)] and minocycline on MMPs' activities were assessed by zymography and TIMPs expression by Western analysis. Morphological damage was quantified by morphometry of hematoxylin and eosin-stained retinal sections. RESULTS: Retinal extracts exhibited activities of proMMP-9 and proMMP-2. The activity of proMMP-9 increased immediately post ischemia (PI) and peaked to 4.6 times that of normal untreated controls in ischemic retinas and to 2.6 times that of controls in retinas of fellow sham-treated eyes at 24 h PI. The relative amount of TIMP-1 increased to 1.9-fold following ischemia and 2.5-fold in fellow sham-treated eyes at 24 h PI. ProMMP-2 activity increased more than two-fold immediately, at 24 h and at 48 h PI in ischemic retinas, and insignificantly in fellow sham-treated eyes. Treatment with 25 mg/kg AG or NNA caused a non-significant increase in proMMP-9 activity at 24 h PI (3.7- and 2.9-fold, respectively, p>0.6). There was no effect of AG or NNA on the activity of proMMP-2. Minocycline significantly attenuated the retinal ischemic damage, primarily by partially preserving ganglion cells and the inner plexiform layer. Minocyline (0.5 mg/ml or 5 mg/ml) inhibited MMPs' activities in ischemic retinal extracts in vitro. CONCLUSIONS: MMPs participated in morphological ischemic damage to rat retina. Treatment with minocycline dramatically attenuated damage to the retina.

Intraoperative complications of phacoemulsification in eyes with and without pseudoexfoliation.

PURPOSE: To determine the intraoperative complications in a large series of phacoemulsification procedures, including patients with and without pseudoexfoliation, excluding those with marked phacodonesis or lens subluxation. SETTING: Department of Ophthalmology, Carmel Medical Centre, Haifa, Israel. METHODS: This institutional case-control study included 1501 consecutive phacoemulsification procedures: 137 eyes with pseudoexfoliation and 1364 eyes without this condition. Baseline demographics and clinical factors were collected from the medical files. A comparative analysis of the incidence of intraoperative complications in eyes with or without pseudoexfoliation was calculated. Univariate analysis and multiple logistic regression were used to identify ocular factors that predicted intraoperative complications. RESULTS: There was no significant difference (P>.05) in the rate of intraoperative complications between the pseudoexfoliation (5.8%) and control (4.0%) groups. There were no significant differences in the incidence of capsular breaks, vitreous loss, and zonular ruptures without vitreous loss in the 2 groups. Pseudoexfoliation did not confer a statistically higher risk for intraoperative complications (odds ratio 1.62, 95% confidence interval 0.74-3.55). CONCLUSION: Phacoemulsification by experienced surgeons is safe in eyes with pseudoexfoliation without marked phacodonesis or lens subluxation.

Long-term intraocular pressure control after clear corneal phacoemulsification in glaucoma patients.

PURPOSE: To evaluate long-term IOP control after sutureless clear corneal phacoemulsification in eyes with preoperatively controlled glaucoma. SETTING: Institutional study. METHODS: The charts of 345 patients who had uneventful sutureless clear corneal phacoemulsification with acrylic foldable lens (IOL) implantation were retrospectively reviewed. Included were 58 patients with medically controlled open-angle glaucoma and 287 normal controls. Follow-up was 1 to 2 years. Outcome measures were postoperative IOP and number of glaucoma medications. RESULTS: Postoperatively, there was an insignificant decrease in IOP in the glaucoma group; the mean decrease was 1.5 mm Hg +/- 4.4 (SD) at 12 months and 1.9 +/- 4.9 mm Hg at 24 months. The mean number of medications decreased significantly at 12 months (0.53 +/- 0.86) and at 24 months (0.38 +/- 0.9) (P=.04). The control group also had a significant decrease in IOP, with a mean decrease of 0.72 +/- 3.7 mm Hg at 12 months (P=.01) and 1.33 +/- 3.2 mm Hg at 24 months (P<.0001). The decrease in IOP was more pronounced in eyes with a higher preoperative IOP in both the glaucoma and control groups. CONCLUSIONS: These findings suggest that sutureless clear corneal phacoemulsification with foldable acrylic IOL implantation is a relatively simple and efficient surgical option in patients with cataract and well-controlled glaucoma. The approach combines long-term IOP control with fewer medications and leads to rapid visual rehabilitation.