Selective Inhibition of Retinal Angiogenesis by Targeting PI3 Kinase

Ocular neovascularisation is a pathological hallmark of some forms of debilitating blindness including diabetic retinopathy, age related macular degeneration and retinopathy of prematurity. Current therapies for delaying unwanted ocular angiogenesis include laser surgery or molecular inhibition of the pro-angiogenic factor VEGF. However, targeting of angiogenic pathways other than, or in combination to VEGF, may lead to more effective and safer inhibitors of intraocular angiogenesis. In a small chemical screen using zebrafish, we identify LY294002 as an effective and selective inhibitor of both developmental and ectopic hyaloid angiogenesis in the eye. LY294002, a PI3 kinase inhibitor, exerts its anti-angiogenic effect in a dose-dependent manner, without perturbing existing vessels. Significantly, LY294002 delivered by intraocular injection, significantly inhibits ocular angiogenesis without systemic side-effects and without diminishing visual function. Thus, targeting of PI3 kinase pathways has the potential to effectively and safely treat neovascularisation in eye disease.

A review on the use of corneal implants for the treatment of presbyopia

In recent years there has seen an increased interest in refractive surgery for the correction of presbyopia. This can be attributed to a number of factors such as the increased demand from patients to have perfect vision without the need for glasses, spurred on by the success of high street refractive laser surgery. Also the World Health Organisation (WHO) estimated in 2005 that over a 1.04 billion people worldwide are affected by presbyopia (Holden et al. 2008). This vast number of people is valued as a potential market and is a huge enticement to the ophthalmic industry to try and develop devices and products to treat this condition. Recent advances in technology have renewed interest in the implantation of corneal inlays for surgical treatment of presbyopia. Dexl et al. (2011) suggest that the reason for this is the further development of biomaterial technology, advances in femtosecond laser and the need for a reversible presbyopic treatment.

Single vocal cord irradiation:a competitive treatment strategy in early glottic cancer

INTRODUCTION: The treatment of choice for early glottic cancer is still being debated; ultimately it relies on the functional outcome. This paper reports on a novel sparing 4D conformal technique for single vocal cord irradiation (SVCI).

MATERIAL AND METHODS: The records of 164 T1a patients with SCC of the vocal cord, irradiated in the Erasmus MC between 2000 and 2008, were analyzed for local control and overall survival. The quality of life was determined by EORTC H&N35 questionnaires. Also the VHI (voice handicap index), and the TSH (thyroid stimulating hormone) blood levels, were established. On-line image guided SVCI, using cone beam CT or stereotactic radiation therapy (SRT) techniques, were developed.

RESULTS: A LC rate at five-years of 93% and a VHI of 12.7 (0-63) was determined. It appeared feasible to irradiate one vocal cord within 1-2mm accuracy. This way sparing of the contralateral (CL) vocal cord and CL normal tissues, could be achieved.

CONCLUSIONS: Given the accuracy (1-2mm) and small volume disease (CTV limited to one vocal cord), for the use of stereotactic RT techniques SVCI with large fraction sizes is currently being investigated in clinic. It is argued that hypofractionated SVCI can be a competitive alternative to laser surgery.

Reversal of optic disc cupping after glaucoma surgery analyzed with a scanning laser tomograph

Objective: To detect and quantitate changes in optic nerve morphology after glaucoma surgery using the Heidelberg Retina Tomograph (HRT, Heidelberg Instruments, Heidelberg, Germany). Design: Nonconsecutive observational case series. Participants and Intervention: The authors prospectively enrolled 21 adult patients undergoing incisional glaucoma surgery for progressive glaucoma damage. Quantitative analysis of the optic nerve head by scanning laser tomography and automated perimetry were performed before and after glaucoma surgery. Main Outcome Measures: Changes in optic nerve parameters were subjected to linear regression analysis with respect to percent of postoperative reduction of intraocular pressure (IOP), as well as with respect to age, refraction, preoperative cup:disc ratio, and change in visual field parameters. Results: Seventeen patients had pre- and postoperative images suitable for analysis. Mean IOP at the time of image acquisition before surgery was 30.5 ± 12 mmHg, and after surgery 11.8 ± 5.2 mmHg (mean follow-up, 26 ± 7 weeks). Eleven of 13 (85%) patients having IOP reduction of greater than 40% showed improvement in optic disc parameters. All four patients with less than 25% reduction in IOP showed worsening of most parameters. Changes in optic disc parameters were highly correlated with percent IOP reduction and with age. The parameters in which change most strongly correlated with percent change of IOP were cup area, rim area, cup:disc ratio, and mean cup depth (each, P <0.005). The age of the patient correlated highly with change in maximum cup depth (P <0.005). Refraction and clinically determined cup:disc ratio correlated poorly with changes in measured optic disc parameters. Clinical improvement in visual fields was correlated with the degree of improvement of cup:disc ratio (P = 0.025). Conclusion: Most patients showing a 40% lowering of IOP after glaucoma surgery show improved optic nerve morphology as measured by the HRT. The amount of improvement correlated highly with the percent reduction of IOP.

Demarcation laser therapy in the management of macular-sparing persistent subretinal fluid after scleral buckling procedures

Background: Persistent or recurrent macular-sparing subretinal fluid (SRF) can sometimes occur following scleral buckling procedures. Observation and reoperation have been used in the management of such cases. Demarcation laser therapy (DLT) has been used to treat macular-sparing retinal detachments in the context of cytomegalovirus retinitis and as primary treatment for selected rhegmatogenous retinal detachments. There are, however, scarce data in the literature regarding its use following primary scleral buckling procedures. The current study explores the use of DLT under the latter circumstances. Methods: The medical records of all consecutive patients with persistent SRF sparing the macula following primary rhegmatogenous retinal detachment repair using a scleral buckling procedure were retrospectively reviewed. Only those patients in whom the breaks were localised to the area of indentation and, thus, seemed to be well supported by the buckle were included. Demographics, clinical characteristics of the retinal detachment prior to scleral buckling, extension of the residual SRF observed postoperatively, details of the laser procedure, anatomical and functional outcomes and complications were evaluated. Results: Seven patients, all females, with a mean age of 47.9 years (range: 20-81) were included in the study. The retinal detachments were superior (n=3), inferior (n=3) and subtotal, affecting both superior and inferior retina (n=1). Scleral buckling procedures were used to treat the retinal detachments in all cases. Following demarcation laser therapy, the area of SRF remained stable in two patients, and flattened in four. In one patient, extension of SRF occurred requiring further surgery. Conclusions: Demarcation laser therapy appears to be a reasonable option in the management of patients with persistent or recurrent SRF sparing the macula following scleral buckling surgery. © Springer-Verlag 2006.

Influence of YAG laser posterior capsulotomy on preexisting glaucoma

Purpose. To evaluate the effects of a YAG laser posterior capsulotomy on intraocular pressure (IOP) in glaucoma patients. Methods. We retrospectively studied 69 patients who underwent posterior capsulotomy following cataract or combined cataract-glaucoma surgery and who had a minimum follow-up of six months. We assessed IOP control, number of glaucoma medications required, and need for additional glaucoma surgery following capsulotomy as clinical outcomes. We defined an "unfavorable result" as: a =5 mm Hg sustained rise in IOP, a need for additional glaucoma medications, and/or a need for additional glaucoma surgery. We calculated Kaplan-Meier event rate curves for these "unfavorable results." Mean follow-up was 24.4 ± 12.3 months. Results. 6.3% of patients had an IOP rise of =5 mm Hg one hour post capsulotomy. The actuarial (Kaplan-Meier) rate of any "unfavorable result" was 11.6% at 4 months, 38.1% at 12 months, 46.1% at 24 months, and 52.1% at 36 months following capsulotomy. Conclusions. Progression of glaucoma after YAG capsulotomy is common and may be accelerated by the laser procedure.

Laser peripheral iridoplasty for angle-closure

BACKGROUND: Angle-closure glaucoma is a leading cause of irreversible blindness in the world. Treatment is aimed at opening the anterior chamber angle and lowering the IOP with medical and/or surgical treatment (e.g. trabeculectomy, lens extraction). Laser iridotomy works by eliminating pupillary block and widens the anterior chamber angle in the majority of patients. When laser iridotomy fails to open the anterior chamber angle, laser iridoplasty may be recommended as one of the options in current standard treatment for angle-closure. Laser peripheral iridoplasty works by shrinking and pulling the peripheral iris tissue away from the trabecular meshwork. Laser peripheral iridoplasty can be used for crisis of acute angle-closure and also in non-acute situations.

OBJECTIVES: To assess the effectiveness of laser peripheral iridoplasty in the treatment of narrow angles (i.e. primary angle-closure suspect), primary angle-closure (PAC) or primary angle-closure glaucoma (PACG) in non-acute situations when compared with any other intervention. In this review, angle-closure will refer to patients with narrow angles (PACs), PAC and PACG.

SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2011, Issue 12), MEDLINE (January 1950 to January 2012), EMBASE (January 1980 to January 2012), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to January 2012), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). There were no date or language restrictions in the electronic searches for trials. The electronic databases were last searched on 5 January 2012.

SELECTION CRITERIA: We included only randomised controlled trials (RCTs) in this review. Patients with narrow angles, PAC or PACG were eligible. We excluded studies that included only patients with acute presentations, using laser peripheral iridoplasty to break acute crisis.

DATA COLLECTION AND ANALYSIS: No analysis was carried out as only one trial was included in the review.

MAIN RESULTS: We included one RCT with 158 participants. The trial reported laser peripheral iridoplasty as an adjunct to laser peripheral iridotomy compared to iridotomy alone. The authors report no superiority in using iridoplasty as an adjunct to iridotomy for IOP, number of medications or need for surgery.

AUTHORS' CONCLUSIONS: There is currently no strong evidence for laser peripheral iridoplasty's use in treating angle-closure.

Impact of posterior subcapsular opacification on vision and visual function among subjects undergoing cataract surgery in rural China: Study of Cataract Outcomes and Up-Take of Services (SCOUTS) in the Caring is Hip Project, report 5.

AIM: To study the effect of posterior capsular opacification (PCO) on vision and visual function in patients undergoing cataract surgery in rural China, and to compare this with the effect of refractive error. METHODS: Patients undergoing cataract surgery in at least one eye by local surgeons in a rural setting between 8 August and 31 December 2005 were examined with slit lamp grading of PCO 10-14 months after surgery. Subjects with any PCO associated with best-corrected visual acuity of 6/7.5 or worse, or with grade 2+ or worse PCO without visual decrement, were offered YAG laser capsulotomy. Vision and self-reported visual function were assessed, and various demographic and clinical factors potentially associated with PCO were recorded. RESULTS: Of 313 patients operated on within the study window, 239 (76%) could be contacted by telephone; study examinations were performed on 176 (74%). Examined subjects had a mean (SD) age of 69.4 (10.5) years, 116 (67%) were female, and 149 (86%) had been blind (presenting visual acuity < or = 6/60) in the operated eye before surgery. PCO of grade 1 or above was present in 34 of 204 operated eyes (16.7%). Those with PCO had significantly worse presenting vision (p = 0.007) but not visual function (p>0.3) than those without PCO. Women had a significantly higher prevalence of PCO (20.9%) than did men (8.6%, p<0.05). Of 19 eyes undergoing capsulotomy with best-corrected visual acuity measured the next day, 13 (68%) improved by one or more lines, and seven (37%) improved by two or more lines. Despite a higher uptake of capsulotomy (95%) as opposed to refraction (35%) in this cohort, the yield in terms of eyes with poor presenting visual acuity (< 6/18) that could be improved was higher for refraction (26% = 9/35) than for capsulotomy (9% = 3/35). CONCLUSION: The prevalence of PCO and impact on vision and visual function in this cohort was modest 1 year after surgery. However, PCO prevalence increases with time. Follow-up of this cohort is underway to determine the effectiveness of this early intervention in identifying and treating subjects who will eventually experience clinically significant PCO.

Effectiveness of diode laser trans-scleral cyclophotocoagulation in patients following silicone oil-induced ocular hypertension in Chinese eyes.

We evaluated the effectiveness of diode laser trans-scleral cyclophotocoagulation (TSCPC) on intraocular pressure (IOP) in nine patients having raised IOP following use of silicone oil (SO) for retinal detachment (RD) surgery in a retrospective observational case series. Diode laser TSCPC was applied at a power setting of 1.75 to 2.5 watts, for two sec with a maximum of 30 applications. The patients were followed up for 40 to 312 weeks. The mean pre-laser IOP was 32.06 mm Hg (SD 7.32). The mean post-laser IOP at one month, three months and six months was 17.89 mm Hg (SD 8.23), 21.89 mm Hg (SD 8.16) and 21.67 mm Hg (SD 7.55) respectively. The final IOP (at the last follow-up) was 19.56 mm Hg (SD 7.85) (P=0.021). Seven of them had undergone SO removal. In our observation, effectiveness of TSCPC in long-term control of SO-induced ocular hypertension was limited as compared to short-term control of IOP.