Reduction in incidence of optic nerve disease with annual ivermectin to control onchocerciasis. Ophthalmological results from a placebo controlled comparative 3-dose ivermectin study in the treatment of onchocerciasis. Effect of single-dose ivermectin therapy on human Onchocerca volvulus infection with onchocercal ocular involvement. The effect of single dose ivermectin alone or in combination with albendazole on Wuchereria bancrofti infection in primary school children in Tanzania. Randomized controlled trial of combined 5-Fluorouracil and low-molecular-weight heparin in the management of unselected rhegmatogenous retinal detachments undergoing primary vitrectomy. Adjuvant 5-fluorouracil and heparin prevents proliferative vitreoretinopathy : Results from a randomized, double-blind, controlled clinical trial. Timolol treatment prevents or delays glaucomatous visual field loss in individuals with ocular hypertension: a five-year, randomized, double-masked, clinical trial. Posterior continuous curvilinear capsulorhexis with and without optic capture of the posterior chamber intraocular lens in the absence of vitrectomy. Intravitreal bevacizumab for surgical treatment of severe proliferative diabetic retinopathy.
The safety and efficacy of ivermectin in the prevention of blindness from onchocerciasis have been established in many studies that have addressed the drug's effects on the front of the eye. We undertook a study with sufficient statistical power to detect an effect on optic nerve disease (OND), probably the main cause of blindness in the disorder. The trial was based in 34 mesoendemic communities in Kaduna State, Nigeria. Villagers aged 5 years and older were randomly assigned annual dosing with ivermectin or placebo for 3 years. Participants underwent medical and ophthalmological examinations before the first, third, and fourth treatments. 3522 villagers aged 15 and older were re-examined at least once. Skin-snip samples were taken at baseline for calculation of microfilarial load. The outcome measure was development of disc pallor accompanied by objective evidence of deterioration in visual function; 116 subjects (45 ivermectin-treated, 71 placebo-treated) showed such changes during the trial. The incidence rate ratio (ivermectin vs placebo) was 0.90 (95% CI 0.54-1.51) for subjects with loads of 0-10 mf (microfilariae) per mg skin and 0.52 (0.29-0.93) for subjects with more than 10 mf/mg. The incidence rate ratio varied little when account was taken of age, sex, presence of pre-existing disc pallor in one eye, previous use of diethylcarbamazine citrate, or doses of ivermectin or placebo received. There was evidence that ivermectin reduced the incidence of OND in subjects with microfilarial loads above 10 mf/mg but had little effect in those with lower loads. Sustained annual delivery of ivermectin could prevent a substantial proportion of onchocercal blindness in mesoendemic communities. One hundred and ninety eight patients with moderate to heavy infection with Onchocerca volvulus and with eye involvement in most, were allocated randomly to treatment with 100, 150 or 200 mcg/kg body weight of ivermectin or placebo given as a single oral dose in a double-blind dose finding study. The patients were drawn from an area under over ten years of vector control in Northern Ghana by the Onchocerciasis Control Programme, OCP. They underwent detailed clinical, laboratory and ophthalmological examination before treatment and in the review period of one year in hospital. Ivermectin given in a dose of 100, 150 or 200 mcg/kg eliminated microfilariae similarly slowly over 3-6 months and was associated with inflammatory reaction in the anterior segment which resolved without treatment. No changes in the fundus of the eye was detected by fluorescein angiography and no no-table other adverse eye reaction was observed. The ceiling of therapeutic activity of ivermectin in the eye is therefore put at 100 mcg/kg which is lower than the level fo 150 mcg/kg found in the skin. The apparent discrepancy may be due to different dose requirements on account of different mechanisms of action of ivermectin at the two sites. In the skin there is active killing while in the eye it is presumed there is a passive elimination of microfilariae. Ivermectin has shown promise as a potentially safe and effective microfilaricidal drug for the treatment of onchocerciasis. Several limited studies have shown it to have fewer side effects, especially ocular complications, than the currently available drug, diethylcarbamazine. The detailed ocular findings in 200 moderately to heavily infected Liberians who were enrolled in a safety and dose-finding study are presented. They received either 0, 100, 150, or 200 micrograms/kg of ivermectin and were followed up for 12 months. In clinical studies so far carried out ivermectin in a dose of 100, 150, or 200 micrograms/kg has not been associated with any major adverse reactions nor were there any sight-threatening effects even in the presence of severe ocular disease. Each of these doses significantly reduced the ocular microfilaria load for at least 12 months when compared with either the placebo (p less than 0.05) or pretreatment values (p less than 0.001). However, the 100 and 150 micrograms/kg doses caused fewer minor side effects than the higher dose. These results confirm that ivermectin in a single oral dose may be a safe and effective microfilaricidal drug for the treatment of onchocerciasis and that it appears to be free of major ocular side effects. Examination of 1829 children from 6 primary schools in coastal Tanzania revealed overall Wuchereria bancrofti microfilaria (mf) and circulating filarial antigen (CFA) prevalences of 17.3% and 43.7%, respectively. A randomized double-blind field trial with a single dose of ivermectin (150-200 microg/kg body weight) alone or in combination with albendazole (400 mg) was subsequently carried out among these children. Both treatment regimens resulted in a considerable decrease in mean mf intensities, with overall reductions being slightly but statistically significantly higher for the combination than for ivermectin alone. The difference in effect between the two treatment regimens was most pronounced at 6 months, whereas it was minor at 12 months after treatment. The relative effect of treatment on mean CFA units was less pronounced than on mf. For both treatment regimens, reductions in CFA intensity appeared to be higher in children who were both CFA and mf positive before treatment, which may suggest that treatment mainly affected the survival and/or production of mf, rather than the survival of adult worms. New cases of infection appeared after treatment with both regimens among the pre-treatment mf and CFA negative children. Adverse reactions were few and mild in both groups, and mainly reported from pre-treatment mf and CFA positive children. The alarmingly high prevalence of W. bancrofti infection in primary school children highlights the importance of also determining the reversibility of already acquired early lesions, and the development of new measures and strategies to specifically protect children from later developing clinical disease. To determine the efficacy of a combination of 5-fluorouracil (5FU) and low-molecular-weight heparin (LMWH) in the treatment of unselected rhegmatogenous retinal detachment (RRD) undergoing primary vitrectomy.
                Double-masked, prospective, randomized, placebo-controlled clinical trial.
                Six hundred forty-one patients presenting with primary RRD were recruited from 2 specialized vitreoretinal units-Moorfields Eye Hospital, London (n = 553) and St. Pauls Eye Unit, Liverpool (n = 88).
                All patients underwent primary vitrectomy and gas endotamponade. Adjuvant therapy in the treatment group consisted of 5 IU/ml LMWH and 200 mug/ml 5FU added to the perioperative infusion fluid.
                The primary outcome measure was retinal reattachment after primary vitrectomy without any reoperations at 6 months. Secondary outcome measures recorded at 6 months were the occurrence and grade of proliferative vitreoretinopathy (PVR), best-corrected visual acuity in logarithm of the minimum angle of resolution, intraocular pressure (mmHg), corneal clarity, and complications.
                The overall primary success rate was 84.4%; in the treatment group, the primary success rate was 82.3% compared with 86.8% in the placebo group (P = 0.12). At 6 months, the final complete anatomical reattachment rate was 97.9% in both treatment and placebo groups. The number of patients who failed due to the development of PVR was not statistically significant, 23 in the treatment group (7.0%) and 14 in the placebo group (4.9%) (P = 0.309). There was no significant difference in the mean visual acuity at 6 months in the placebo group (0.48) versus the treatment group (0.53; P = 0.072). The visual acuity at 6 months of patients presenting with a macula-sparing retinal detachment was significantly worse in the treatment group (P = 0.0091). There was no significant difference between the 2 groups in patients who presented with a macula involving retinal detachment (P = 0.896).
                Primary vitrectomy has a high anatomic and visual success rate for RRD. Adjuvant therapy with 5FU and LMWH does not improve the anatomic or visual success rate of unselected primary retinal detachments undergoing vitrectomy. After adjuvant therapy, a worse visual outcome was observed in patients presenting with macula-sparing retinal detachments. A combination of 5FU and LMWH should not be used routinely for primary RRD surgery. To assess the safety and efficacy of adjuvant combination therapy using 5-fluorouracil (5-FU) and low molecular weight heparin (LMWH) for prevention of proliferative vitreoretinopathy (PVR) after vitrectomy and retinal reattachment surgery.
                Prospective randomized, double-masked, placebo controlled trial.
                One hundred seventy-four high-risk patients were randomized to receive either 5-FU and LMWH therapy or placebo. Patients were selected from all patients undergoing primary vitrectomy for rhegmatogenous retinal detachment.
                Results of standard surgery with 5-FU and LMWH therapy or placebo were compared at the 6-month follow-up.
                Development of postoperative PVR, retinal reattachment at 6 months after surgery, single operation reattachment rate, number of reoperations, and best-corrected visual acuity.
                There were 87 patients in the 5-FU and LMWH therapy group and 87 in the placebo group. The incidence of postoperative PVR was significantly lower (P = 0.02) in the 5-FU and LMWH therapy compared with the placebo group. In 26.4% (23/87) of the placebo group and in 12.6% (11/87) of the 5-FU and LMWH group, postoperative PVR developed. In the 5-FU and LMWH group, the number of patients undergoing more than one operation was 19.5% (17/87) and the number of reoperations resulting from PVR was 52.9% (9/17). In the placebo group, the number of patients undergoing more than one operation was 25.3% (22/87) and the number of reoperations resulting from PVR was 72.7% (16/22). The difference in visual acuity was not statistically different in the two treatment groups, although those patients in whom postoperative PVR developed tended to have poorer vision (P < 0.0001). There were no differences in complication rates between the two groups.
                There is a significant reduction in the incidence of postoperative PVR in patients receiving the 5-FU and LMWH therapy and in the reoperation rate resulting from PVR. This trial shows that incidence of PVR can be reduced with inexpensive and simple pharmacologic treatment with 5-FU and LMWH and should be used routinely in the treatment of patients at risk of developing PVR. A 5-year, randomized, double-masked, clinical trial was conducted to determine whether treatment with topical timolol maleate was effective in preventing or delaying the onset of glaucomatous visual field loss in subjects with ocular hypertension. Sixty-five individuals considered to be at moderate risk for developing open-angle glaucoma were recruited for the study. In each patient, one eye was chosen randomly to receive timolol twice-daily while the fellow eye received diluent (placebo). Timolol administration reduced IOP from baseline in the treated eyes over the course of the study by a mean +/- SD of 4.9 +/- 3.4 mm Hg. Timolol administration also produced a mean +/- SD contralateral reduction of IOP from baseline in the untreated fellow eyes of 2.9 +/- 3.1 mm Hg. The mean +/- SD difference in IOP between the treated and untreated eyes during the study was 2.3 +/- 2.6 mm Hg. Over the course of the study reproducible visual field loss developed in 4 timolol treated eyes and 10 placebo treated eyes (P = .039, McNemar test). Clinical progressive optic disc cupping was noted in four treated and eight untreated eyes (P = .11, McNemar test). In the 42 subjects who completed a minimum 4-year follow-up, baseline and final optic disc photographs were analyzed using a computer image analysis system to determine changes in the area of disc pallor. The mean +/- SD increase in optic disc pallor was 0.86% +/- 2.4% in the timolol treated eyes and 1.80% +/- 3.6% in the placebo treated eyes. This difference was statistically significant (P = .04, paired t-test). This study provides evidence that medical treatment prevents or delays the onset of glaucomatous visual field loss and optic disc damage in individuals with ocular hypertension. The magnitude of the protective effect of timolol was partially obscured by the contralateral reduction of IOP in the placebo treated fellow eyes. To evaluate the efficacy of posterior continuous curvilinear capsulorhexis (PCCC) with optic capture of the posterior chamber intraocular lens (PC IOL) in the absence of vitrectomy in preventing secondary opacification of the visual axis following pediatric cataract surgery.
                Thirty-four eyes of 28 children with congenital or developmental cataract, aged 1.5 to 12 years (mean, 6.39 years), were included in this prospective, randomized study. Anterior continuous curvilinear capsulorhexis (ACCC) with PCCC without optic capture of the PC IOL was performed in group A (18 eyes) and ACCC with PCCC with optic capture of the PC IOL was performed in group B (16 eyes). None of the eyes underwent anterior vitrectomy. Secondary opacification of the visual axis, visual acuity, and possible complications were observed and analyzed.
                The follow-up period ranged from 8 to 28 months (mean, 17.5 months). All 16 eyes (100%) in group B had a clear visual axis at the end of follow-up. Eight eyes (44.4%) in group A had significant opacification of the visual axis. The difference between the two groups was statistically significant (P = .0011). No eye in group B required secondary intervention, whereas all 8 eyes in group A with significant secondary opacification required secondary intervention. There was no statistically significant difference in other complications such as anterior chamber reaction, fibrin formation, lenticular precipitates, and posterior synechiae. The final best-corrected visual acuity at the end of follow-up was comparable in the two groups (P > .05).
                PCCC with optic capture of the PC IOL prevents secondary opacification of the visual axis even in the absence of vitrectomy. The purpose of this study is to evaluate the role, the safety and the effectiveness of intravitreal bevacizumab (IVB) injections as an adjunct to vitrectomy in the management of severe proliferative diabetic retinopathy (PDR).
                Case-Control Study
                Randomized controlled trial performed on 72 eyes of 68 patients affected by vitreous haemorrhage (VH) and tractional retinal detachment (TRD), which occurred as a consequence of active proliferative diabetic retinopathy (PDR). We randomly assigned eligible patients in a 1: 1: 1 ratio to receive a sham injection or an intravitreal injection of 1.25 mg of bevacizumab, either 7 or 20 days before the vitrectomy. In order to obtain three homogeneous groups of surgical complexity, we assigned to the following preoperative parameters a score from 0 to 3: a) vitreous haemorrhage, b) prior retinal laser-photocoagulation, c) morphological types of retinal detachment such as focal, hammock, central diffuse, table-top. Complete ophthalmic examinations and color fundus photography were performed at baseline and 1, 6, 12, and 24 weeks after the surgery.
                Intraoperative management, safety, efficacy of IVB at different time injection as an adjunct to vitrectomy in the management of severe PDR RESULTS: Group A (sham injection): intraoperative bleeding occurred in 19 cases (79.1%), the use of endodiathermy was necessary in 13 patients (54.1%), relaxing retinotomy was performed on one patient (4.1%), and in four cases (16.6%) iatrogenic retinal breaks occurred. The surgical mean time was 84 minutes (SD 12 minutes). Group B (bevacizumab administered 7 days before vitrectomy): intraoperative bleeding occurred in two cases (8.3%) and the use of endodiathermy was necessary in two patients (8.3%). No iatrogenic breaks occurred during the surgery. The surgical mean time was 65 minutes (SD 18 minutes). Group C (bevacizumab administered 20 days before vitrectomy): intraoperative bleeding occurred in three cases (12.5%), the use of endodiathermy was necessary in three patients (1.5%), and an iatrogenic break occurred in one patient (4.1%) while the delamination of fibrovascular tissue was being performed. The surgical mean time was 69 minutes (SD 21 minutes). The average difference in the surgical time was statistically significant between group A and group B (p = 0.025), and between group A and group C (p = 0.031). At the end of the surgery, the retina was completely attached in all eyes. At the 6-month follow-up, we observed the development of tractional retinal detachment (TRD) in one out of 24 patients from group C (4%).
                A preoperative intravitreal injection of bevacizumab may represent a new strategy for the surgical treatment of severe PDR by reducing retinal and iris neovascularization: this would make surgery much easier and safer, thus improving the anatomical and functional prognosis. According to our study, the best surgical results are achieved performing the IVB 7 days preoperatively.
The lack of evidence for prevention of visual impairment and blindness should not be interpreted to mean that ivermectin is not effective, however, clearly this is a key question that remains unanswered. The main evidence for a protective effect of mass treatment with ivermectin on visual field loss and optic nerve disease comes from communities mesoendemic for the savannah strain of O.volvulus. Whether these findings can be applied to communities with different endemicity and affected by the forest strain is unclear. Serious adverse effects were rarely reported. None of the studies, however, were conducted in areas where people are infected with Loa loa (loiasis).