Combined orbital irradiation and systemic steroids compared with systemic steroids alone in the management of moderate-to-severe Graves' ophthalmopathy: a preliminary study. Randomized trial of intravitreal bevacizumab alone or combined with triamcinolone versus macular photocoagulation in diabetic macular edema. Intravitreal bevacizumab with or without triamcinolone for refractory diabetic macular edema; a placebo-controlled, randomized clinical trial. Randomized prospective comparison of visian toric implantable collamer lens and conventional photorefractive keratectomy for moderate to high myopic astigmatism. Effects of intravenous methylprednisolone on outcome in MRI-based prognostic subgroups in acute optic neuritis. Intravitreal triamcinolone acetonide for diffuse diabetic macular oedema: 6-month results of a prospective controlled trial. A prospective, comparative study between endoscopic cyclophotocoagulation and the Ahmed drainage implant in refractory glaucoma. A randomized controlled clinical trial on the efficacy of radiation therapy in the control of subfoveal choroidal neovascularization in age-related macular degeneration: radiation versus observation. [Acyclovir and trifluorothymidine in herpetic kerato-uveitis. A comparative clinical study. Indications for corticoid therapy].
To assess the efficacy and safety of combined orbital irradiation and systemic steroids in the management of moderate-to-severe Graves' ophthalmopathy.
                Single-blind randomised prospective study.
                Regional hospital, Hong Kong.
                Sixteen patients with active moderate-to-severe Graves' ophthalmopathy who were randomly assigned to steroid therapy (ST group) or combination therapy of orbital irradiation and systemic steroids (SRT group) between June 2000 and June 2003.
                NOSPECS scoring system, total eye score, subjective eye score, and extra-ocular muscle thickness as determined by either computed tomographic or magnetic resonance imaging scans.
                The study was completed by 15 of 16 patients. Both groups experienced improvement in total eye score, soft tissue swelling, ocular motility, visual acuity, and subjective eye score at 52-week follow-up. Total eye score improved earlier in the SRT group, achieving statistical significance (P<0.05) at as early as 4 weeks of follow-up. Improvement in ocular parameters was greater and led to a significantly greater reduction in total eye score than in the ST group at weeks 16, 24, and 52. Maximum extra-ocular muscle thickness was significantly reduced in the SRT group only. No change was observed in proptosis in either group. No serious adverse effect was observed with the addition of orbital irradiation to steroid therapy.
                A combination of orbital irradiation and systemic steroids is well tolerated and more effective than steroids alone in the treatment of active moderate-to-severe Graves' ophthalmopathy. It achieves greater and more rapid improvement in soft tissue swelling, ocular motility, and visual acuity. To compare the results of intravitreal bevacizumab (IVB) injection alone or in combination with intravitreal triamcinolone acetonide (IVT) versus macular laser photocoagulation (MPC) as a primary treatment of diabetic macular edema (DME).
                Randomized 3-arm clinical trial.
                A total of 150 eyes of 129 patients with clinically significant DME and no previous treatment.
                The eyes were randomly assigned to 1 of the 3 study arms: the IVB group, patients who received 1.25 mg IVB (50 eyes); the IVB/IVT group, patients who received 1.25 mg of IVB and 2 mg of IVT (50 eyes); and the MPC group, patients who underwent focal or modified grid laser (50 eyes). Retreatment was performed at 12-week intervals whenever indicated.
                Change in best-corrected visual acuity (VA) at week 24.
                VA changes among the groups were statistically significant at 6 (P<0.001) and 24 (P = 0.012) weeks. The significant treatment effect was demonstrated in the IVB group at all follow-up visits and in the IVB/IVT group at 6 and 12 weeks. VA changes +/- standard deviation at 36 weeks were -0.28+/-0.25, -0.04+/-0.33, and +0.01+/-0.27 logarithm of minimum angle of resolution in the IVB, IVB/IVT, and MPC groups, respectively (P = 0.053). Significant central macular thickness (CMT) reduction was observed in all groups only up to 6 weeks; however, CMT changes were not significant among the groups in all visits. Overall, retreatment was required for 27 eyes up to 36 weeks (14 in the IVB group, 10 in the IVB/IVT group, and 3 in the MPC group). In the IVB group, in which a greater VA improvement was observed, only 1 injection was required in 72% of the cases. VA improvement >2 Snellen lines at 36 weeks was detected in 37%, 25%, and 14.8% of patients in the IVB, IVB/IVT, and MPC groups, respectively.
                Intravitreal bevacizumab injection in patients with DME yielded a better visual outcome at 24 weeks compared with macular photocoagulation. A change in CMT beyond the 6-week time point that corresponded to the vision change was not detected. No adjunctive effect of IVT was demonstrated.
                The author(s) have no proprietary or commercial interest in any materials discussed in this article. To evaluate the effect of three intravitreal injections of bevacizumab (IVB) alone or combined with triamcinolone (IVT) in the first injection for treatment of refractory diabetic macular edema (DME).
                In this prospective, placebo-controlled, randomized clinical trial, 115 eyes of 101 patients with refractory DME were included. Subjects were randomly assigned to one of the three study arms: 1) three injections of IVB (1.25 mg/0.05 ml) at 6-week intervals, 2) combined IVB and IVT (1.25 mg/0.05 ml and 2 mg/0.05 ml respectively) followed by two injections of IVB at 6-week intervals, and 3) sham injection (control group). The primary outcome measure was change in central macular thickness (CMT). Secondary outcome measures were change in best-corrected logMAR visual acuity (BCVA ) and incidence of potential adverse events.
                Central macular thickness was reduced significantly in both the IVB and IVB/IVT groups. At week 24, CMT change compared to the baseline was -95.7 microm (95% CI, -172.2 to -19.26) in the IVB group, -92.1 microm (95% CI, -154.4 to -29.7) in the IVB/IVT group, and 34.9 microm (95% CI, 7.9 to 61.9) in the control group. There was a significant difference between the IVB and control groups (P = 0.012) and between the IVB/IVT and control groups (P = 0.022). Improvement of BCVA was initiated at weeks 6 and 12 in the IVB/IVT and IVB groups respectively. In terms of BCVA change compared to the baseline at 24 weeks, the differences between the IVB and control groups (P = 0.01) and also between the IVB/IVT and control groups (P = 0.006) were significant. No significant differences were detected in the changes of CMT and BCVA between the IVB and IVB/IVT groups (P = 0.99). Anterior chamber reaction was noticed in eight (19.5%) and seven (18.9%) eyes respectively in the IVB and IVB/IVT groups the day after injection, and it resolved with no sequel. Elevation of IOP occurred in three eyes (8.1%) in the IVB/IVT group.
                Three consecutive intravitreal injections of bevacizumab had a beneficial effect on refractory DME in terms of CMT reduction and BCVA improvement. Addition of triamcinolone in the first injection seemed to induce earlier visual improvement; however, it did not show any significant additive effect later during follow-up. To compare the Visian Toric Implantable Collamer Lens (TICL), a toric phakic intraocular lens (IOL), and photorefractive keratectomy (PRK) in the correction of moderate to high myopic astigmatism.
                This prospective, randomized study consisted of 43 eyes implanted with the TICL (20 bilateral cases) and 45 eyes receiving PRK with mitomycin C (22 bilateral cases) with moderate to high myopia (-6.00 to -20.00 diopters [D] sphere) measured at the spectacle plane and 1.00 to 4.00 D of astigmatism. All patient treatment and follow-up occurred at the Naval Medical Center San Diego. Study follow-up was 1 day, 1 week, 1, 3, 6, and 12 months postoperative.
                Mean best spectacle-corrected visual acuity (BSCVA), change in BSCVA, proportion of cases with improvement of 1 or more lines of BSCVA, proportion of cases with BSCVA and uncorrected visual acuity (UCVA) 20/12.5 or better, proportion of cases with BSCVA and UCVA 20/16 or better (6 months, 88% vs 54%, P=.002), and predictability +/-1.00 D (6 months, 100% vs 67%, P<.001) were all significantly better in the TICL group than the PRK group at all time periods studied postoperatively. Similarly, contrast sensitivity, tested at both the 5% photopic level and the 25% mesopic level, was significantly better at all postoperative time points in the TICL group. Mean spherical equivalent refraction was closer to emmetropia (0.28+/-0.41 vs 0.76+/-0.86, P=.005), and predictability +/-0.50 D and stability of manifest refraction (+/-0.50 D and +/-1.00 D) were significantly better in the TICL group at all postoperative visits through 6 months. Mean astigmatism correction at 6 months was not significantly different between the two groups (0.52+/-0.33 vs 0.46+/-0.35, P=.450).
                The TICL performed better than PRK in all measures of safety (BSCVA), efficacy (UCVA), predictability, and stability in this comparison, supporting the TICL as a viable alternative to existing refractive surgical treatments. Treatment of acute optic neuritis with steroids has been shown to hasten visual recovery without affecting the final degree of recovery. However, MRI-clinical studies indicate that patients with long optic nerve lesions, particularly those that involve the nerve within the optic canal, may have a worse prognosis for recovery of vision. Partly because such lesions could lead to swelling and subsequent ischemic optic nerve damage, steroids could have a selective beneficial effect on this subgroup of patients. The present randomized trial was designed to test this possibility. Sixty-six patients with acute optic neuritis received IV saline or IV methylprednisolone. The clinical, psychophysical, electrophysiologic, and MRI outcomes were assessed after 6 months. Patients with short lesions presented earlier than those with long lesions (involving three or more 5-mm-thick slices of any part of the optic nerve, as well as its intracanalicular portion), and lesion length was significantly less in patients presenting within a week of onset of symptoms. Lesions also tended to lengthen during follow-up in individual patients. Treatment did not limit lesion length in either the long or short lesion subgroup and had no significant effect on final visual outcome. We conclude that steroids do not improve visual outcome or lesion length in patients with acute optic neuritis. To evaluate prospectively the efficacy and safety of one intravitreal injection of 4 mg triamcinolone acetonide for refractory diffuse diabetic macular edema.
                Seventeen patients with bilateral diabetic macular edema unresponsive to laser photocoagulation. In all patients, one eye was injected, and the other served as a control. The intervention consisted in intravitreal injection of 4 mg triamcinolone acetonide. The main outcome measure was central macular thickness (CMT) at 4, 12 and 24 weeks, measured by Optical Coherence Tomography. Secondary outcomes were Early Treatment Diabetic Rentinopathy Study (ETDRS) scores, intraocular pressure and cataract PROGRESSION.
                Before injection, mean +/- SD CMT was 566.4 +/- 182.4 mum in injected eyes. Four, 12, and 24 weeks after injection, it was 228.4 +/- 47.5 mum, 210.9 +/- 87.2 mum and 358.5 +/- 160.5 mum respectively. CMT was significantly lower in injected eyes vs. control eyes except 24 weeks after injection because of a recurrence of macular edema in 9/17 injected eyes. Mean +/- SD gain in ETDRS score was significantly better in injected eyes vs. control eyes 4, 12 and 24 weeks after TA injection. In 9 of the 17 injected eyes, intraocular pressure exceeded 24 mmHg and was controlled by topical medication.
                In the short-term, intravitreal injection of triamcinolone effectively reduces macular thickening due to diffuse diabetic macular edema and improves visual acuity in most cases. The long-term effect of this treatment and predictive factors of visual recovery remain to be elucidated. To compare endoscopic cyclophotocoagulation (ECP) and the Ahmed drainage implant in the treatment of refractory glaucoma.
                Sixty-eight eyes of 68 patients with refractory glaucoma were prospectively assigned to either ECP or Ahmed tube shunt implantation. All procedures were performed by a single surgeon. Eyes that were included were pseudophakic with a history of at least one trabeculectomy with antimetabolite, an intraocular pressure (IOP) equal to or above 35 mm Hg on maximum tolerated medical therapy, and a visual acuity better than light perception. Exclusion criteria included eyes that had had previous glaucoma drainage device implantation or a cyclodestructive procedure. Success was defined as an IOP more than 6 mm Hg and less than 21 mm Hg, with or without topical anti-hypertensive therapy.
                The mean follow-up was 19.82 +/- 8.35 months and 21.29 +/- 6.42 months, for the Ahmed and ECP groups, respectively (P = 0.4). The preoperative IOP, 41.32 +/- 3.03 mm Hg (Ahmed) and 41.61 +/- 3.42 mm Hg (ECP) (P = 0.5), and the mean postoperative IOP, at 24 months follow-up, 14.73 +/- 6.44 mm Hg (Ahmed) and 14.07 +/- 7.21 mm Hg (ECP) (P = 0.7), were significantly different from baseline in both groups (P < 0.001). Kaplan-Meier survival curve analysis showed a probability of success at 24 months of 70.59% and 73.53% for the Ahmed and ECP groups, respectively (P = 0.7). Complications included choroidal detachment (Ahmed 17.64%, ECP 2.94%), shallow anterior chamber (Ahmed 17.64%, ECP 0.0%), and hyphema (Ahmed 14.7%, ECP 17.64%).
                There was no difference in the success rate between the Ahmed Glaucoma Valve and ECP in refractory glaucoma. The eyes that underwent Ahmed tube shunt implantation had more complications than those treated with ECP. The results of several pilot studies concerning radiation therapy for age-related subfoveal choroidal neovascularization (CNV) have been published recently. Although positive treatment results have been described, it is not known whether this therapy alters the natural course of eyes with neovascular age-related macular degeneration (AMD). A randomized controlled clinical trial was conducted in which radiation therapy was compared with observation in patients with subfoveal neovascular AMD.
                Seventy-four patients with a recent drop in central vision due to subfoveal age-related CNV were randomized to either radiation treatment or observation. Patients with either classic, occult or mixed type CNV were included. Eyes in the treatment group received a radiation dose of 24 Gy in four fractions of 6 Gy. Evaluation of data concerning visual acuity (VA) and fluorescein angiography occurred at 3, 6 and 12 months after inclusion.
                At 12 months of follow-up 52.2% of the observation group versus 32.0% of the irradiation group had lost 3 or more lines of VA (P = 0.03, log rank test). More severe visual decline, 6 lines or more, was observed in 40.9% of the observation versus 8.8% in the irradiation group (P = 0.002 using log rank test). At 12 months 39.6% of the observation group and 20.0% of the treatment group had VA of less than 0.1 (P = 0.08, log rank test). The size of the CNV membrane doubled in 25.2% of eyes in the observation group versus 20.0% in the treatment group at least 12 months (P = 0.5, log rank test). No side effects were observed.
                Preservation of VA was significantly better in the treatment group compared with the control group at 12 months. Nevertheless we noted a drop in central vision of 3 or more lines in a substantial proportion of the treatment group. Radiation therapy does not prevent visual loss in all patients with age-related subfoveal CNV, and whether the treatment benefit at 12 months will persist has to be awaited. The relative efficacy of aciclovir (ACV) and trifluorothymidine (TFT) was evaluated in a randomized, open clinical trial of 37 patients with herpetic kerato-uveitis. Twenty-one patients were treated with ACV and 16 with TFT. Topical steroids were withheld as long as the degree of inflammation permitted. Although both drugs were effective in healing the herpetic corneal ulcers, TFT had a significantly shorter healing time than ACV. However, ACV was more effective in treating the iridocyclitis than TFT. In 5 cases the keratouveitis responded to ACV alone, while only one case was successfully managed with TFT alone. Both drugs seemed to prevent steroid-induced epithelial complications and no significant side-effects were observed with either drug. The treatment of herpetic keratouveitis with single agents such as ACV and TFT is dependent upon rapidly instituting therapy and minimizing the use of topical steroids. The apparently good intraocular penetration of ACV and TFT may decrease the need for adjunctive steroid therapy and thereby minimize the risks of facilitated viral replication and steroid-dependence.
RCTs included in this review suggest that steroids placed inside the eye by either intravitreal injection or surgical implantation may improve visual outcomes in eyes with persistent or refractory DME. Since the studies in our report focused on chronic or refractory DME, the question arises whether intravitreal steroids therapy could be of value in other stages of DME, especially the earlier stages either as standalone therapy or in combination with other therapies, such as laser photocoagulation.