Iridocyclectomy for neovascular glaucoma caused by proton-beam radiotherapy of pigmented ciliary adenocarcinoma.

PURPOSE: To report neovascular glaucoma after proton-beam radiotherapy of an adenocarcinoma of the pigmented ciliary epithelium and its successful treatment by iridocyclectomy. PATIENT AND METHODS: A 65-year-old man developed neovascular glaucoma 10 months after proton-beam radiotherapy of a small pigmented iridociliary tumour with a clinical differential diagnosis of uveal melanoma or adenocarcinoma. The diagnosis of 'toxic tumour syndrome' was made, and iridocyclectomy performed. RESULTS: Histopathology and immunohistochemistry of the specimen diagnosed an adenocarcinoma of the pigmented ciliary epithelium, with the presence of mitoses suggesting residual viable tumour cells. The rubeosis regressed, with normalization of the intraocular pressure. Phacoemulsification for radiation-induced cataract restored VA to 6/9, which was better than that recorded at initial referral, the patient having longstanding cellophane maculopathy. CONCLUSIONS: Neovascular glaucoma after radiotherapy of a small, pigmented, ciliary body tumour raises the possibility of adenocarcinoma. This 'toxic tumour syndrome' may respond to iridocyclectomy of the irradiated tumour.

Controlled delivery of 5-chlorouracil using poly(ortho esters) in filtering surgery for glaucoma.

PURPOSE: To evaluate the antimitotic and toxic effects of 5-chlorouracil (5-CU) and 5-fluorouracil (5-FU) and study their potential to delay filtering bleb closure in the rabbit eye when released by poly(ortho esters) (POE). METHODS: Rabbit Tenon fibroblasts and human conjunctival cells were incubated with various 5-CU and 5-FU concentrations. Antiproliferative effects and toxicity were evaluated at 24 and 72 hours by monotetrazolium, neutral red, and Hoechst tests and cell counting. Mechanisms of cell death were evaluated using TUNEL assay, annexin V binding, immunohistochemistry for anti-apoptosis-inducing factor (AIF) and LEI/L-DNase II. Trabeculectomy was performed in pigmented rabbits. Two hundred microliters of POE loaded with 1% wt/wt 5-FU or 5-CU was injected into the subconjunctival space after surgery. Intraocular pressure (IOP) and bleb persistence were monitored for 150 days. RESULTS: In vitro, 5-FU showed a higher antiproliferative effect and a more toxic effect than 5-CU. 5-FU induced cell necrosis, whereas 5-CU induced mostly apoptosis. The apoptosis induced by 5-CU was driven through a non-caspase-dependent pathway involving AIF and LEI/L-DNase II. In vivo, at 34 days after surgery, the mean IOP in the POE/5-CU-treated group was 83% of the baseline level and only 40% in the POE/5-FU-treated group. At 100 days after surgery, IOP was still decreased in the POE/5-CU group when compared with the controls and still inferior to the preoperative value. The mean long-term IOP, with all time points considered, was significantly (P < 0.0001) decreased in the POE/5-CU-treated group (6.0 +/- 2.4 mm Hg) when compared with both control groups, the trabeculectomy alone group (7.6 +/- 2.9 mm Hg), and the POE alone group (7.5 +/- 2.6 mm Hg). Histologic analysis showed evidence of functioning blebs in the POE-5-CU-treated eyes along with a preserved structure of the conjunctiva epithelium. CONCLUSIONS: The slow release of 5-CU from POE has a longstanding effect on the decrease of IOP after glaucoma-filtering surgery in the rabbit eye. Thus, the slow release of POE/5-CU may be beneficial for the prevention of bleb closure in patients who undergo complicated trabeculectomy.

Intravitreal Dexamethasone Implant for the Treatment of Macular Edema after Retinal Vein Occlusion in a Clinical Setting.

Background: To study the efficacy and safety of a new intravitreal implant (sustained release of dexamethasone, Ozurdex®) recently approved in Switzerland for the treatment of macular edema secondary to retinal vein occlusion in a clinical setting.Patients and Methods: Prospective non-consecutive study of patients with macular edema secondary to central retinal vein occlusion or branch retinal vein occlusion treated with implant of dexamethasone 0.7 mg. Follow-up visits were performed at day 1, week 1 and monthly thereafter. ETDRS best corrected visual acuity, Goldmann tonometry and macular thickness on SD-OCT were registered. Retreatment was carried out on a pro re nata basis starting from month 3.Results: Fifteen eyes of 15 patients were included (8 branch retinal vein occlusions, 7 central retinal vein occlusions). 33 % of the patients achieved 3 lines or more of vision gain. The central retinal vein occlusion subgroup showed a mean decline in visual acuity at month 3. A reduction of 36 % of macular edema was already observed at day 1. All maculae were dry at month 1. The mean time of recurrence of macular edema for both groups was 4.6 months. A similar reduction of macular edema was obtained after a second implantation. An intraocular pressure increase of ≥ 20 % was observed after the first implantation in 53 % of patients.Conclusion: Our study showed efficacy and safety of intravitreal dexamethasone implant in the treatment of macular edema due to retinal vein occlusion. Anatomical efficacy was observed at day 1 but seems to have shorter effect than previously published data. No serious side effects were observed.

Four years later: a clinical update on latanoprost.

PURPOSE: Almost five years have elapsed since the introduction of latanoprost on several markets and considering the large number of publications dealing with it, the authors felt that it was worth re-evaluating the drug. METHODS: The criterion used to select trials for inclusion in the review was: all articles mentioning the drug in common electronic data-bases; these were then screened and considered, on the basis of methodological quality. RESULTS: Experimental data suggest that latanoprost acts by remodeling the extracellular matrix in the ciliary muscle, thus increasing the flow of aqueous humor through the ciliary muscle bundles of the uveoscleral pathway. POAG: Latanoprost persistently improves the pulsatile ocular blood flow in primary open angle glaucoma (POAG). Recent trials confirmed the greater IOP-lowering efficacy of latanoprost vs. timolol, dorzolamide, brimonidine and unoprostone. Trials lasting up to 24 months showed that latanoprost is effective in long-term treatment of POAG and ocular hypertension (OH), with no signs of loss of efficacy when compared to timolol or dorzolamide. Latanoprost provides better control of circadian IOP. Non-responders to beta-blockers should preferably be switched to latanoprost monotherapy before a combination therapy is started. The possibility of a fixed combination of latanoprost and timolol has been explored, with promising results. NTG: Latanoprost is effective in normal tension glaucoma (NTG), lowering IOP, improving pulsatile ocular blood flow and increasing ocular perfusion pressure. OTHER GLAUCOMAS: Latanoprost may provide effective IOP control in angle-closure glaucoma after iridectomy, in pigmentary glaucoma, glaucoma after cataract extraction and steroid-induced glaucoma. However, latanoprost was effective in only a minority of pediatric cases of glaucoma and is contraindicated in all forms of uveitic glaucoma. SAFETY: In the articles reviewed, new or duration-related adverse events were reported.

Early effects of intravitreal triamcinolone on macular edema: mechanistic implication.

PURPOSE: To evaluate the early effects of intravitreal triamcinolone acetonide (TA) on cystoid macular edema associated with retinal vein occlusion and diabetic retinopathy. DESIGN: Prospective, interventional, small case series. PARTICIPANTS: Four patients with cystoid macular edema resulting from retinal vein occlusion or diabetic retinopathy of more than 4 months' duration and evaluated as suitable for treatment with intravitreous injection of TA. METHODS: After ophthalmic examination, including visual acuity assessment, intraocular pressure (IOP) measurement, and optical coherence tomography (OCT) analysis, the patients received a single intravitreal injection of 4 mg TA. After the injection, consecutive visual acuity assessment, IOP measurement, and OCT analysis were performed after 1 hour, 6 hours, 1 week, and 2 weeks. MAIN OUTCOME MEASURE: Optical coherence tomography assessment of macular thickness. RESULTS: Macular thickness and edema initially were reduced as early as 1 hour after TA injection. A further continuous decrease was observed during the 2 weeks after treatment. CONCLUSIONS: This rapid effect of intravitreal TA is interpreted to indicate that nongenomic effects on retinal or retinal pigment epithelial cell membranes, or both, may be responsible for this phenomenon. Identifications of these mechanisms may help design alternative, more specific drugs for the treatment of macular edema.

Reconditioning of the trabeculo-descemet's membrane with the 532-nm Nd : YAG (SLT) laser after deep sclerectomy.

The purpose of this study was to evaluate the intraocular pressure (IOP)-lowering effect of modified goniopuncture with the 532-nm Nd : YAG selective laser trabeculoplasty (SLT) laser on eyes after deep sclerectomy with collagen implant (DSCI). This was an interventional cased series. The effects of modified goniopuncture on eyes with insufficient IOP-lowering after DSCI were observed. Goniopuncture was performed using a Q-switched, frequency-doubled 532-nm Nd : YAG laser (SLT-goniopuncture, SLT-G). Outcome measures were amount of IOP-lowering and rapidity of decrease after laser intervention. In all, 10 eyes of 10 patients with a mean age of 71.0±7.7 (SD) years were treated with SLT-G. The mean time of SLT-G after DSCI procedure was 7.1±10.9 months. SLT-G decreased IOP from an average of 16.1±3.4 mm Hg to 14.2±2.8 mm Hg (after 15 min), 13.6±3.9 mm Hg (at 1 day), 12.5±4.1 mm Hg (at 1 month), and 12.6±2.5 (at 6 months) (P<0.0125). There were no complications related to the intervention. Patients in this series achieved an average 22.5% of IOP reduction after SLT-G. The use of the SLT laser appears to be an effective and safe alternative to the traditional Nd : YAG laser for goniopuncture in eyes after DSCI, with potential advantages related to non-perforation of trabeculo-descemet's membrane (TDM).

Dexamethasone intravitreal implant for noninfectious intermediate or posterior uveitis.

OBJECTIVE: To evaluate the safety and efficacy of 2 doses of dexamethasone intravitreal implant (DEX implant) for treatment of noninfectious intermediate or posterior uveitis. METHODS: In this 26-week trial, eyes with noninfectious intermediate or posterior uveitis were randomized to a single treatment with a 0.7-mg DEX implant (n = 77), 0.35-mg DEX implant (n = 76), or sham procedure (n = 76). MAIN OUTCOME MEASURE: The main outcome measure was the proportion of eyes with a vitreous haze score of 0 at week 8. RESULTS: The proportion of eyes with a vitreous haze score of 0 at week 8 was 47% with the 0.7-mg DEX implant, 36% with the 0.35-mg DEX implant, and 12% with the sham (P < .001); this benefit persisted through week 26. A gain of 15 or more letters from baseline best-corrected visual acuity was seen in significantly more eyes in the DEX implant groups than the sham group at all study visits. The percentage of eyes with intraocular pressure of 25 mm Hg or more peaked at 7.1% for the 0.7-mg DEX implant, 8.7% for the 0.35-mg DEX implant, and 4.2% for the sham (P > .05 at any visit). The incidence of cataract reported in the phakic eyes was 9 of 62 (15%) with the 0.7-mg DEX implant, 6 of 51 (12%) with the 0.35-mg DEX implant, and 4 of 55 (7%) with the sham (P > .05). CONCLUSIONS: In patients with noninfectious intermediate or posterior uveitis, a single DEX implant significantly improved intraocular inflammation and visual acuity persisting for 6 months. Application to Clinical Practice Dexamethasone intravitreal implant may be used safely and effectively for treatment of intermediate and posterior uveitis. Trial Registration clinicaltrials.gov Identifier: NCT00333814.

Long-term results of deep sclerectomy with collagen implant.

PURPOSE: To study prospectively the success rate and complications of deep sclerectomy with collagen implant (DSCI). SETTING: Glaucoma Unit, Department of Ophthalmology, Hôpital Ophtalmique Jules Gonin, University of Lausanne, Lausanne, Switzerland. METHODS: This nonrandomized prospective trial comprised 105 eyes of 105 patients with medically uncontrolled primary and secondary open-angle glaucoma. Visual acuity, intraocular pressure (IOP), and slitlamp examinations were performed before surgery and after surgery at 1 and 7 days, and 1, 3, 6, 9, 12, 18, 24, 30, 36, 48, 54, 60, 66, 72, 78, 84, 90, and 96 months. Visual field examinations were repeated every 6 months. RESULTS: Mean follow-up period was 64 months +/- 26.6 (SD). Mean preoperative IOP was 26.8 +/- 7.7 mm Hg, and mean postoperative IOP was 5.2 +/- 3.35 mm Hg at day 1 and 12 +/- 3 mm Hg at month 78. At 96 months, the qualified success rate (ie, patients who achieved IOP <21 mm Hg with and without medication) was 91%, and the complete success rate (ie, IOP <21 mm Hg without medication) was 57%. At 96 months, 34% of patients had an IOP <21 mm Hg with medication. Fifty-one patients (49%) achieved an IOP < or =15 mm Hg without medication. Neodymium:YAG goniopuncture was performed in 54 patients (51%); mean time of goniopuncture performance was 21 months, and mean IOP before goniopuncture was 20 mm Hg, dropping to 11 mm Hg after goniopuncture. No shallow or flat anterior chamber, endophthalmitis, or surgery-induced cataract was observed. However, 26 patients (25%) showed a progression of preexisting senile cataract (mean time 26 months; range 18 to 37 months). Injections of 5-fluorouracil were administered to 25 patients (23%) who underwent DSCI to salvage encysted blebs. Mean number of medications per patient was reduced from 2.3 +/- 0.7 to 0.5 +/- 0.7 (signed rank P<.0001). CONCLUSION: Deep sclerectomy with collagen implant appears to provide stable and reasonable control of IOP at long-term follow-up with few immediate postoperative complications.

A new poly(ortho ester)-based drug delivery system as an adjunct treatment in filtering surgery.

PURPOSE: Pharmacologic modulation of wound healing after glaucoma filtering surgery remains a major clinical challenge in ophthalmology. Poly(ortho ester) (POE) is a bioerodible and biocompatible viscous polymer potentially useful as a sustained drug delivery system that allows the frequency of intraocular injections to be reduced. The purpose of this study was to determine the efficacy of POE containing a precise amount of 5-fluorouracil (5-FU) in an experimental model of filtering surgery in the rabbit. METHODS: Trabeculectomy was performed in pigmented rabbit eyes. An ointmentlike formulation of POE containing 1% wt/wt 5-FU was injected subconjunctivally at the site of surgery, during the procedure. Intraocular pressure (IOP), bleb persistence, and ocular inflammatory reaction were monitored until postoperative day 30. Quantitative analysis of 5-FU was performed in the anterior chamber. Histologic analysis was used to assess the appearance of the filtering fistula and the polymer's biocompatibility. RESULTS: The decrease in IOP from baseline and the persistence of the filtering bleb were significantly more marked in the 5-FU-treated eyes during postoperative days 9 through 28. Corneal toxicity triggered by 5-FU was significantly lower in the group that received 5-FU in POE compared with a 5-FU tamponade. Histopathologic evaluation showed that POE was well tolerated, and no fibrosis occurred in eyes treated with POE containing 5-FU. CONCLUSIONS: In this rabbit model of trabeculectomy, the formulation based on POE and containing a precise amount of 5-FU reduced IOP and prolonged bleb persistence in a way similar to the conventional method of a 5-FU tamponade, while significantly reducing 5-FU toxicity.

Evaluation of an intravitreal fluocinolone acetonide implant versus standard systemic therapy in noninfectious posterior uveitis.

PURPOSE: To evaluate the safety and efficacy of an intravitreal fluocinolone acetonide (FA) implant compared with standard therapy in subjects with noninfectious posterior uveitis (NIPU). DESIGN: Randomized, controlled, phase 2b/3, open-label, multicenter superiority trial. PARTICIPANTS: Subjects with unilateral or bilateral NIPU. METHODS: One hundred forty subjects received either a 0.59-mg FA intravitreal implant (n = 66) or standard of care (SOC; n = 74) with either systemic prednisolone or equivalent corticosteroid as monotherapy (> or =0.2 mg/kg daily) or, if judged necessary by the investigator, combination therapy with an immunosuppressive agent plus a lower dose of prednisolone or equivalent corticosteroid (> or =0.1 mg/kg daily). MAIN OUTCOME MEASURES: Time to first recurrence of uveitis. RESULTS: Eyes that received the FA intravitreal implant experienced delayed onset of observed recurrence of uveitis (P<0.01) and a lower rate of recurrence of uveitis (18.2% vs. 63.5%; P< or =0.01) compared with SOC study eyes. Adverse events frequently observed in implanted eyes included elevated intraocular pressure (IOP) requiring IOP-lowering surgery (occurring in 21.2% of implanted eyes) and cataracts requiring extraction (occurring in 87.8% of phakic implanted eyes). No treatment-related nonocular adverse events were observed in the implant group, whereas such events occurred in 25.7% of subjects in the SOC group. CONCLUSIONS: The FA intravitreal implant provided better control of inflammation in patients with uveitis compared with systemic therapy. Intraocular pressure and lens clarity of implanted eyes need close monitoring in patients receiving the FA intravitreal implant.

Résultats à deux ans de la trabéculoplastie sélective au laser dans le glaucome à angle ouvert et l'hypertonie oculaire

BACKGROUND: Selective laser trabeculoplasty (SLT) is a relatively new treatment strategy for the treatment of glaucoma. Its principle is similar to that of argon laser trabeculoplasty (ALT), but may lead to less damage to the trabecular meshwork. METHODS: We assessed the 2-year efficacy of SLT in a noncomparative consecutive case series. Any adult patient either suspected of having glaucoma or with open-angle glaucoma, whose treatment was judged insufficient to reach target intraocular pressure (IOP), could be recruited. IOP and number of glaucoma treatments were recorded over 2 years after the procedure. RESULTS: Our sample consisted of 44 consecutive eyes of 26 patients, aged 69+/-8 years. Eyes were treated initially on the lower 180 degrees . Three of them were retreated after 15 days on the upper 180. Fourteen eyes had ocular hypertension, 17 primary open-angle/normal-tension glaucoma, 11 pseudoexfoliation (PEX) glaucoma, and two pigmentary glaucoma. Thirty-six eyes had previously been treated and continued to be treated with topical anti-glaucoma medication, ten had had prior ALT, nine iridotomy, and 12 filtering surgery. The 2-year-follow up could not be completed for eight eyes because they needed filtering surgery. In the remaining 36 eyes, IOP decreased by a mean of 17.2%, 3.3 mmHg, (19.2+/-4.7 to 15+/-3.6 mmHg) after 2 years (p<0.001). As a secondary outcome, the number of glaucoma treatments decreased from 1.44 to 1.36 drops/patient. Other results according to subgroups of patients are analyzed: the greatest IOP decrease occurred in eyes that had never been treated with anti-glaucoma medication or with PEX glaucoma. SLT was probably valuable in a few eyes after filtering surgery; however, the statistical power of the study was not strong enough to draw a firm conclusion. When expressed in survival curves after 2 years, however, only 48% and 41% of eyes experienced a decrease of more than 3 mmHg or more than 20% of preoperative intraocular pressure, respectively. CONCLUSION: SLT decreases IOP somewhat for at least 2 years without an increase in topical glaucoma treatment. However, it cannot totally replace topical glaucoma treatment. In the future, patient selection should be improved to decrease the cost/effectiveness ratio.

A clinical study of annular cyclitis.

PURPOSE: To investigate six cases of annular cyclitis. METHODS: All patients with impairment of visual acuity underwent complete ophthalmologic examination, color fundus photography, laboratory tests and fluorescein angiography. Indocyanine green (ICG) angiography and B-scan ultrasonography were also performed in three cases in order to diagnose the disease. RESULTS: All patients presented a unilateral or bilateral granulomatous uveitis, associated with inflammatory annular cyclitis. They had a shallow anterior chamber, a mildly elevated intraocular pressure (under 25 mm Hg) and an annular serous retinal detachment. A resolution was observed after specific therapy associated with systemic prednisolone therapy and antiglaucomatous drops. CONCLUSION: This is the first description of an observational study of six patients with inflammatory annular cyclitis.

Baerveldt implant in refractory glaucoma: long-term results and factors influencing outcome.

PURPOSE: To evaluate the clinical outcome of patients who received a Baerveldt implant for refractory glaucoma and to identify factors which may influence the outcome. METHODS: Retrospective study including 51 eyes of 51 patients with medically uncontrolled glaucoma who underwent Baerveldt implant surgery between June 1994 and December 1998. Criteria for success were intraocular pressure (IOP) < or = 21 mmHg and > 6 mmHg, necessity of further antiglaucoma medications, absence of additional glaucoma surgery and no loss of light perception. RESULTS: Over a mean follow-up of 37.6 (SD: +/-18.8) months, the mean intraocular pressure decreased from 34.8 (+/-12.5) mmHg to 14.0 (+/-4.3) mmHg at month 60. Qualified success rate, achieved when IOP was below 21 mmHg and higher than 6 mmHg with medications was 25/48 (52%), complete success rate (same IOP limits without medication) was 14/48 (29%). Seven eyes had major complications or lost light perception. Postoperative visual acuity improved or remained within one Snellen line of the preoperative visual acuity in 35 patients (73%). Factors associated with a better prognosis were a preoperative visual acuity better than 20/400 and etiology of glaucoma. CONCLUSION: The Baerveldt implant is effective in lowering intraocular pressure in most patients with refractory glaucoma. Long-term results are promising with satisfactory IOP control.

T-Flux implant versus Healon GV in deep sclerectomy.

PURPOSE: To compare the efficacy and safety of T-Flux implant versus Healon GV in deep sclerectomy. METHODS: Randomized prospective trial of 23 eyes of 20 patients with medically uncontrolled open angle glaucoma over a period of 24 months, who underwent deep sclerectomy with either Healon GV or T-Flux implant. RESULTS: Mean postoperative intraocular pressure was 13.2 +/- 3.0 mm Hg with T-Flux implant (group 1) and 12.2 +/- 3.5 mm Hg with Healon GV (group 2), with a pressure reduction of 53.0% in group 1 (13.2 mm Hg vs. 28.1 mm Hg) and of 48.1% in group 2 (12.2 mm Hg vs. 23.5 mm Hg). Qualified and complete successes were 100% and 95.4% respectively. Pressures equal to or less than 15 mm Hg were 81.8% in group 1 and 90.9% in group 2 with or without treatment, and 63.6% in group 1 and 81.8% in group 2 without treatment. The number of glaucoma treatments dropped from 2.5 +/- 0.9 to 0.4 +/- 0.7 in group 1 and from 2.2 +/- 1.0 to 0.2 +/- 0.4 in group 2. The goniopuncture rate was 63.6% in group 1 and 36.4% in group 2, with a mean pressure drop of 6.1 +/- 3.9 mm Hg and 3.25 +/- 1.2 mm Hg respectively. Overall, slit-lamp diagnosed surgery-related complications included positive Seidel (13.6%), hyphaema (22.7%), choroidal detachment, and iris incarceration (4.5% each). At 2 years, ultrasound biomicroscopy showed mainly low reflective (40.1%) and flattened (36.4%) blebs. Principally latter ones were associated with the need for adjunctive treatment. A hypoechoic area in the suprachoroidal space was seen in at least 59.1% of eyes at 2 years and was not associated with lower intraocular pressure. CONCLUSION: Deep sclerectomy is an effective and safe surgery. However, longer follow up and larger study groups are required to assess the additional benefit of nonabsorbable implants.

JNK Inhibition Reduced Retinal Ganglion Cell Death after Ischemia/Reperfusion In Vivo and after Hypoxia In Vitro.

Mitogen-activated protein kinases (MAPKs) are key regulators that have been linked to cell survival and death. Among the main classes of MAPKs, c-jun N-terminal kinase (JNK) has been shown to mediate cell stress responses associated with apoptosis. In Vitro, hypoxia induced a significant increase in 661W cell death that paralleled increased activity of JNK and c-jun. 661W cells cultured in presence of the inhibitor of JNK (D-JNKi) were less sensitive to hypoxia-induced cell death. In vivo, elevation in intraocular pressure (IOP) in the rat promoted cell death that correlated with modulation of JNK activation. In vivo inhibition of JNK activation with D-JNKi resulted in a significant and sustained decrease in apoptosis in the ganglion cell layer, the inner nuclear layer and the photoreceptor layer. These results highlight the protective effect of D-JNKi in ischemia/reperfusion induced cell death of the retina.