Clement K. Chan

A Randomized Trial Comparing the Efficacy and Safety of Intravitreal Triamcinolone With Observation to Treat Vision Loss Associated With Macular Edema Secondary to Central Retinal Vein Occlusion: The Standard Care vs Corticosteroid for Retinal Vein Occlusion (SCORE) Study Report 5

OBJECTIVE To compare the efficacy and safety of 1-mg and 4-mg doses of preservative-free intravitreal triamcinolone with observation for eyes with vision loss associated with macular edema secondary to perfused central retinal vein occlusion (CRVO). METHODS Multicenter, randomized, clinical trial of 271 participants. MAIN OUTCOME MEASURE Gain in visual acuity letter score of 15 or more from baseline to month 12. RESULTS Seven percent, 27%, and 26% of participants achieved the primary outcome in the observation, 1-mg, and 4-mg groups, respectively. The odds of achieving the primary outcome were 5.0 times greater in the 1-mg group than the observation group (odds ratio [OR], 5.0; 95% confidence interval [CI], 1.8-14.1; P = .001) and 5.0 times greater in 4-mg group than the observation group (OR, 5.0; 95% CI, 1.8-14.4; P = .001); there was no difference identified between the 1-mg and 4-mg groups (OR, 1.0; 95% CI, 0.5-2.1; P = .97). The rates of elevated intraocular pressure and cataract were similar for the observation and 1-mg groups, but higher in the 4-mg group. CONCLUSIONS Intravitreal triamcinolone is superior to observation for treating vision loss associated with macular edema secondary to CRVO in patients who have characteristics similar to those in the SCORE-CRVO trial. The 1-mg dose has a safety profile superior to that of the 4-mg dose. Application to Clinical Practice Intravitreal triamcinolone in a 1-mg dose, following the retreatment criteria applied in the SCORE Study, should be considered for up to 1 year, and possibly 2 years, for patients with characteristics similar to those in the SCORE-CRVO trial. Trial Registration clinicaltrials.gov Identifier: NCT00105027.

Retinal pigment epithelial tears after intravitreal bevacizumab injection for neovascular age-related macular degeneration.

Purpose: To study retinal pigment epithelium (RPE) tears after off-label intravitreal bevacizumab (Avastin; Genentech, Inc., South San Francisco, CA) injection for neovascular age-related macular degeneration. Eyes with a vascularized pigment epithelial detachment (PED) that developed an RPE tear were compared with eyes with a vascularized PED but without an RPE tear. Methods: Nine retina specialists across the United States and in Europe participated in this retrospective case series. All eyes that received intravitreal bevacizumab injection for choroidal neovascularization (CNV) over 12 months (October 2005 to September 2006) were included. Eyes without all three confirmed tests (fluorescein angiography, fundus photography, and optical coherence tomography) were excluded from analysis. Statistical analyses were performed on multiple characteristics of eyes with a vascularized PED that did and did not develop an RPE tear. Results: Among 2,785 intravitreal bevacizumab injections for 1,064 eyes, RPE tears were found in 22 eyes in 22 patients (2.2%). A vascularized PED was present in 21 of 22 eyes that developed an RPE tear (17.1% of PED eyes; 15, 100% occult CNV; 6, predominantly occult CNV). Mean interval from bevacizumab injections to RPE tears was 37.3 days. Mean follow-up time was 124.9 days. Mean subfoveal PED size was larger for eyes with tears than for those without tears (13.97 mm2 vs 9.9 mm2, respectively; P = 0.01; odds ratio, 1.09). There was substantially smaller mean ratio of CNV size to PED size for eyes with tears than for those without tears (27.9% vs 67.6%, respectively; P = 0.005). Mean pre–bevacizumab injection best-corrected Snellen visual acuity was 20/162, and mean post–RPE tear best-corrected visual acuity was 20/160 (P = 0.48). Conclusion: Large PED size is a predictor for RPE tears, and a small ratio of CNV size to PED size (<50%) is more common in eyes with RPE tears. Vision may be preserved despite RPE tears.

The Question of Ocular Tolerance to Intravitreal Liquid Silicone: A Long-term Analysis

The authors report a retrospective review of 407 eyes that received intravitreal liquid silicone between 1961 and 1984. Initial anatomical success was noted in 270 eyes (66.3%), while initial functional success was achieved in 103 eyes (25.3%). Ten years postoperatively, approximately half of the eyes with initial functional success still had functional vision (49.2%). These eyes had less advanced proliferative vitreoretinopathy and fewer inferior breaks than others. Recurrent retinal detachment rather than late complications was the predominant cause of functional failure in those eyes losing functional vision in less than ten years postoperatively. Late complications were common and frequently required therapeutic intervention. Intravitreal liquid silicone was of great benefit to many monocular patients, but of little benefit to the binocular patients in our series.

An improved technique for management of dislocated posterior chamber implants.

Many techniques for repositioning dislocated posterior chamber implants described in the recent literature involve intricate intraocular manipulation of a needle or other sharp instrument. The author describes an improved sulcus fixation technique, which combines the best features of external and internal approaches. Its main features involve temporary externalization of the haptics for easy and secured placement of suture knots, and subsequent reinternalization of the same haptics through horizontal sclerotomies directly external to the ciliary sulcus for precise fixation of the dislocated posterior chamber implant with consistency. Between May 1989 and December 1990, this technique was successfully used for posterior chamber intraocular lens repositioning in 12 cases. The main advantages of this technique include: (1) easy suture placement, (2) less chance of suture slippage with the secured knots, and (3) avoidance of difficult intraocular maneuvers and possible tissue injury. This improved technique expedites the process of posterior chamber implant repositioning.

Pneumatic Retinopexy for the Repair of Retinal Detachments: A Comprehensive Review (1986–2007)

Pneumatic retinopexy has become an important surgical technique in the modern era of retinal surgical management for retinal detachments. It is primarily indicated for uncomplicated retinal detachments with retinal breaks involving the superior 8 clock hours of the fundus, although more complex retinal detachments may be successfully managed with this technique on a selected basis. Qualified candidates must be willing to maintain a specific head posture for five or more days for optimal outcome with pneumatic retinopexy. Basic surgical steps of pneumatic retinopexy include retinopexy of retinal breaks with cryotherapy or laser, intraocular gas injection before or after retinopexy, and maintenance of proper head posture by the patient for the required time period after surgery. Phakic eyes fared better than nonphakic eyes for pneumatic retinopexy, with the single-operation successes of 71-84% for the former and 41-67% for the latter. Despite lower single-operation successes with pneumatic retinopexy in comparison to sclera buckling, the multicenter pneumatic retinopexy trial and other published reports have shown that the final anatomical and visual outcomes are not disadvantaged by the initial pneumatic retinopexy. An extensive discussion of complications associated with pneumatic retinopexy is presented. In addition, a key feature of this review is a comprehensive update in the outcome of pneumatic retinopexy in published reports from 1986 to the present in chronological order not available in the current literature. This comprehensive summary shows updated average surgical outcomes for the 4,138 eyes in the 21-year period to be similar to previous reports: single-operation successes (74.4%), final operation successes (96.1%), new retinal breaks (11.7%), and proliferative vitreoretinopathy (5.2%).

Optical coherence tomography-measured pigment epithelial detachment height as a predictor for retinal pigment epithelial tears associated with intravitreal bevacizumab injections.

Purpose: The purpose was to study preinjection optical coherence tomography–related factors in age-related macular degeneration eyes with retinal pigment epithelial detachment (PED) that may predispose retinal pigment epithelial (RPE) tears associated with intravitreal bevacizumab injections. Methods: This multicenter retrospective case series involving 9 retina specialists and 7 centers investigated Stratus optical coherence tomography (Carl Zeiss Meditec, Dublin, CA) parameters in eyes with vascularized PED (vPED) from February 2006 to February 2007. Of the 1,280 eyes in 1,255 patients receiving 2,890 intravitreal injections, there were 125 eyes with vPED. For every vPED eye that developed an RPE tear (Group 1), 3 or more vPED eyes without RPE tears (Group 2) were randomly selected in each study center during the same time period for comparison. The primary outcome measure was PED height (&mgr;m), and the secondary measures included volume index (vPED height × surface area), total macular volume, subretinal fluid, cystoid macular edema, center-point thickness, central 1 mm, and pre- and postinjection best-corrected Snellen visual acuities. Results: Twenty-one vPED eyes in 21 patients among 125 vPED eyes (16.8% of all vPED eyes) developed RPE tears. The 21 Group 1 eyes were compared with the 78 randomly selected Group 2 eyes. The vPED height was significantly higher for Group 1 eyes in comparison to Group 2 eyes (mean: 648.9 ± 245.0 vs. 338.1 ± 201.6 &mgr;m, P < 0.001). The same was true for the following: volume index (P = 0.001), subretinal fluid (P = 0.002), and total macular volume (P = 0.04). The mean preinjection and post-RPE tear best-corrected visual acuity were 0.92 logMAR (20/166) and 0.84 logMAR (20/137), respectively (P = 0.25). Multivariate analysis showed PED height to be the only significant risk factor associated with RPE tears in Group 1 eyes [odds ratio = 0.995 (95% confidence interval: 0.992–0.997), P < 0.001]. Conclusion: Elevated preinjection vPED height is the single most significant predictor for RPE tears after bevacizumab injections for vPED eyes. A vPED height >400 &mgr;m is associated with a significant risk for such a complication.

Treatment of Idiopathic Macular Holes by Induced Posterior Vitreous Detachment

PURPOSE To determine if an expansile gas bubble can relieve vitreofoveal traction without vitrectomy by inducing a posterior vitreous detachment (PVD) in eyes with an idiopathic impending or full-thickness macular hole (stages 1-3). The status of the impending and full-thickness macular holes after gas injection and tamponade also was studied secondarily. METHODS Eighteen patients participated in this pilot study. Eleven patients with an impending macular hole (stages 1A and 1B) and seven patients (8 eyes) with a full-thickness macular hole (stages 2 and 3) received gas injections and prospectively were followed for an average of 15.6 months (range, 3-42 months). RESULTS A complete PVD was achieved in 18 of 19 eyes without a prior PVD within 2 to 9 weeks after gas injection. Ten of the 11 impending holes (all 7 had stage 1A holes; 3 of 4 had stage 1B holes) resolved after gas injection. After gas tamponade, three of six early full-thickness (stage 2) macular holes closed. None of the stage 3 macular holes closed after gas injection. The mean best-corrected visual acuity of the successful eyes was 20/32. There were no major complications. CONCLUSION An expansile gas bubble consistently can induce a PVD in aging eyes. The ability of an expansile gas bubble to induce a PVD with minimal morbidity and expense may have clinical applications for macular hole therapy. Impending macular holes may resolve and some early full-thickness (stage 2) macular holes may close after gas injection and tamponade without vitrectomy. The efficacy and safety of this procedure may be evaluated further in the context of a carefully designed prospective and randomized study for selected patients with an idiopathic impending or early macular hole.

Exploratory Analysis of the Effect of Intravitreal Ranibizumab or Triamcinolone on Worsening of Diabetic Retinopathy in a Randomized Clinical Trial

IMPORTANCE The standard care for proliferative diabetic retinopathy (PDR) usually is panretinal photocoagulation, an inherently destructive treatment that can cause iatrogenic vision loss. Therefore, evaluating the effects of therapies for diabetic macular edema on development or worsening of PDR might lead to new therapies for PDR. OBJECTIVE To evaluate the effects of intravitreal ranibizumab or triamcinolone acetonide, administered to treat diabetic macular edema, on worsening of diabetic retinopathy. DESIGN Exploratory analysis was performed on worsening of retinopathy, defined as 1 or more of the following: (1) worsening from no PDR to PDR, (2) worsening of 2 or more severity levels on reading center assessment of fundus photographs in eyes without PDR at baseline, (3) having panretinal photocoagulation, (4) experiencing vitreous hemorrhage, or (5) undergoing vitrectomy for the treatment of PDR. SETTING Community- and university-based ophthalmology practices. PARTICIPANTS Individuals with central-involved diabetic macular edema causing visual acuity impairment. INTERVENTIONS Eyes were assigned randomly to sham with prompt focal/grid laser, 0.5 mg of intravitreal ranibizumab with prompt or deferred (≥24 weeks) laser, or 4 mg of intravitreal triamcinolone acetonide with prompt laser. MAIN OUTCOMES AND MEASURES Three-year cumulative probabilities for retinopathy worsening. RESULTS For eyes without PDR at baseline, the 3-year cumulative probabilities for retinopathy worsening (P value comparison with sham with prompt laser) were 23% using sham with prompt laser, 18% with ranibizumab with prompt laser (P = .25), 7% with ranibizumab with deferred laser (P = .001), and 37% with triamcinolone with prompt laser (P = .10). For eyes with PDR at baseline, the 3-year cumulative probabilities for retinopathy worsening were 40%, 21% (P = .05), 18% (P = .02), and 12% (P < .001), respectively. CONCLUSIONS AND RELEVANCE Intravitreal ranibizumab appears to be associated with a reduced risk of diabetic retinopathy worsening in eyes with or without PDR. Intravitreal triamcinolone also appears to be associated with a reduced risk of PDR worsening. These findings suggest that use of these drugs to prevent worsening of diabetic retinopathy may be feasible. Given the exploratory nature of these analyses, the risk of endophthalmitis following intravitreal injections, and the fact that intravitreal triamcinolone can cause cataract or glaucoma, use of these treatments to reduce the rates of worsening of retinopathy, with or without PDR, does not seem warranted at this time.

Subretinal fibrosis in central serous chorioretinopathy

PURPOSE To report unusual and heretofore unreported visually damaging manifestations of severe central serous chorioretinopathy. METHODS Case studies. RESULTS Each of six male patients (average age, 40 years) had a form of severe central serous chorioretinopathy with at least one eye containing fibrin in the subretinal space that then developed into a subretinal fibrotic scar. Scar formation was followed by a tenting up of the macula, vascularization of the fibrosis (subretinal neovascularization), or a retinal pigment epithelial rip. Four of the seven eyes with subretinal fibrosis had severe visual loss (20/400 or worse). CONCLUSION Subretinal fibrin and other extracellular matrix molecules appear to stimulate the retinal pigment epithelium to undergo fibrous metaplasia, which results in subretinal fibrotic scar formation and other sequelae, all of which can lead to severe visual loss.

Prospective evaluation of the incidence and risk factors for the development of RPE tears after high- and low-dose ranibizumab therapy.

Purpose: To prospectively determine the incidence and risk factors for retinal pigment epithelial (RPE) tears in eyes with vascularized pigment epithelial detachments (PED) and exudative age-related macular degeneration receiving antivascular endothelial growth factor therapy. Methods: Eyes were prospectively randomized into 1 of 4 arms: 1) 0.5 mg of ranibizumab monthly for 12 months; 2) 0.5 mg of ranibizumab monthly for 3 months and then pro re nata on the basis of clinical and optical coherence tomography–guided indications; 3) high-dose 2.0 mg of ranibizumab monthly for 12 months; or 4) 2.0 mg of ranibizumab monthly for 3 months and then pro re nata thereafter. All PEDs were measured for height, greatest linear diameter, and surface area at baseline. The incidence of RPE tears in the entire 4-arm cohort was determined at the end of 12 months. Eyes were divided into two groups (tear vs. nontear) and statistically compared to determine risk factors for the development of RPE tear. Results: Of 37 eyes, a total of 5 developed postranibizumab RPE tears during the course of the study (incidence 14%). Four of the 5 tears occurred in the high-dose 2.0-mg groups. Baseline PED height, surface area, and greatest linear diameter were significantly greater in the group that developed RPE tears versus the nontear group (P = 0.018, 0.031, and 0.048, respectively). There were significantly more eyes with PED height >550 microns in the RPE tear group (4 of 5, 80%) compared with the nontear group (9 of 32, 18%) (P = 0.042). The presence of PED height >550 microns was associated with an increased tear rate from 14% to 31%. Furthermore, retrospective identification of a ring sign or Grade 1 tear at baseline, in addition to PED height >550 microns, was associated with a further increase in the tear rate to 67%. Conclusion: In this study, the prospective incidence of RPE tears was ∼14%. A baseline PED height >550 microns and presence of a Grade 1 tear, or positive ring sign, were identified as high-risk factors for the subsequent development of an RPE tear.