Macular Degeneration: Chan CK

Scott IU, Bressler NM, Bressler SB, Browning DJ, Chan CK, Danis RP, Davis MD, Kollman C, Qin H, Anonymous00398. · Pennsylvania State University College of Medicine, Hershey, PA, USA. · Retina. · Pubmed #18185135 links to  free full text

Abstract: PURPOSE: To evaluate agreement in diabetic retinopathy severity classification by retina specialists performing ophthalmoscopy versus reading center (RC) grading of seven-field stereoscopic fundus photographs in a phase 2 clinical trial of intravitreal bevacizumab for center-involved diabetic macular edema. METHODS: Clinicians' grading scale used four levels: microaneurysms only, mild/moderate nonproliferative diabetic retinopathy (NPDR), severe NPDR, and proliferative diabetic retinopathy (PDR) or prior panretinal photocoagulation (PRP) or both. The RC scale used eight levels: microaneurysms only, mild NPDR, moderate NPDR, moderately severe NPDR, severe NPDR, mild PDR, moderate PDR, and high-risk PDR. Percent agreement and kappa statistic were defined by collapsing RC categories to match those used by clinicians. RESULTS: There was agreement in 89/118 eyes (75%) with kappa = 0.55 (95% confidence interval [0.41, 0.68]). In six eyes, disagreements were of potential substantial clinical importance: five eyes with subtle retinal neovascularization and one with a small preretinal hemorrhage identified only in photographs. CONCLUSIONS: Clinician grading of retinopathy severity had moderate agreement with RC grading and might be useful for placing eyes into broad baseline categories.

Anonymous00409, Scott IU, Edwards AR, Beck RW, Bressler NM, Chan CK, Elman MJ, Friedman SM, Greven CM, Maturi RK, Pieramici DJ, Shami M, Singerman LJ, Stockdale CR. · Jaeb Center for Health Research, 15310 Amberly Drive, Suite 350, Tampa, FL 33647, USA. · Ophthalmology. · Pubmed #17698196 links to  free full text

Abstract: OBJECTIVE: To provide data on the short-term effect of intravitreal bevacizumab for diabetic macular edema (DME). DESIGN: Randomized phase II clinical trial. PARTICIPANTS: One hundred twenty-one eyes of 121 subjects (109 eligible for analysis) with DME and Snellen acuity equivalent ranging from 20/32 to 20/320. INTERVENTIONS: Random assignment to 1 of 5 groups: (A) focal photocoagulation at baseline (n = 19), (B) intravitreal injection of 1.25 mg of bevacizumab at baseline and 6 weeks (n = 22), (C) intravitreal injection of 2.5 mg of bevacizumab at baseline and 6 weeks (n = 24), (D) intravitreal injection of 1.25 mg of bevacizumab at baseline and sham injection at 6 weeks (n = 22), or (E) intravitreal injection of 1.25 mg of bevacizumab at baseline and 6 weeks with photocoagulation at 3 weeks (n = 22). MAIN OUTCOME MEASURES: Central subfield thickness (CST) on optical coherence tomography and best-corrected visual acuity (VA) were measured at baseline and after 3, 6, 9, 12, 18, and 24 weeks. RESULTS: At baseline, median CST was 411 mum and median Snellen VA equivalent was 20/50. Compared with group A, groups B and C had a greater reduction in CST at 3 weeks and about 1 line better median VA over 12 weeks. There were no meaningful differences between groups B and C in CST reduction or VA improvement. A CST reduction > 11% (reliability limit) was present at 3 weeks in 36 of 84 (43%) bevacizumab-treated eyes and 5 of 18 (28%) eyes treated with laser alone, and at 6 weeks in 31 of 84 (37%) and 9 of 18 (50%) eyes, respectively. Combining focal photocoagulation with bevacizumab resulted in no apparent short-term benefit or adverse outcomes. Endophthalmitis developed in 1 eye. The following events occurred during the first 24 weeks in subjects treated with bevacizumab without attributing cause to the drug: myocardial infarction (n = 2), congestive heart failure (n = 1), elevated blood pressure (n = 3), and worsened renal function (n = 3). CONCLUSION: These results demonstrate that intravitreal bevacizumab can reduce DME in some eyes, but the study was not designed to determine whether treatment is beneficial. A phase III trial would be needed for that purpose.

Chan CK, Fan DS, Chan WM, Lai WW, Lee VY, Lam DS. · Department of Ophthalmology & Visual Sciences, The Chinese University of Hong Kong, Hong Kong Eye Hospital, Kowloon, Hong Kong. · Eye. · Pubmed #15184946 No free full text.

Abstract: PURPOSE: To assess the intraocular pressure (IOP) and corneal endothelial changes, over a 6-month period, after a single injection of intravitreal triamcinolone (ivTA) in Chinese patients. METHODS: A total of 43 eyes of 43 consecutive Chinese patients with various macular diseases received a single bolus injection of 4 mg ivTA, of which, 14 eyes with significant cataracts underwent simultaneous phacoemulsification and primary intraocular lens implantation. IOP was measured preoperatively and weekly in the first month, and then monthly until 6 months postinjection. Specular microscopy was performed on 24 of the 29 eyes without simultaneous cataract surgery, preoperatively and at months 1, 3, and 6. RESULTS: All patients completed 6 months of follow-up. Nine out of 43 (20.9%) eyes had IOP >21 mmHg. Their mean maximum IOP was 29.2 mmHg (range 23.0-37.0), necessitating the use of 2.0 types of topical antiglaucomatous medications on average. The IOP elevation occurred at a mean of 5.2 weeks (range 1-17) postinjection. All IOPs returned to normal, without additional antiglaucomatous medications, by 6 months. There was no statistically significant difference (paired t-test, P<0.05) in the corneal endothelial cell count and other specular microscopy parameters up to 6 months after the injections. CONCLUSION: A single 4 mg bolus injection of ivTA appeared to have no harmful effects on the corneal endothelium. IvTA caused transient IOP elevations in 20.9% of Chinese patients, similar to that observed in Caucasians. As the IOP rise can occur as early as 1 week after the injection, early monitoring will help its early detection and prevent optic nerve damage.

Lam DS, Lai TY, Lee VY, Chan CK, Liu DT, Mohamed S, Li CL. · Department of Ophthalmology and Visual Sciences, Chinese University of Hong Kong, Hong Kong. · Retina. · Pubmed #19287286 No free full text.

Abstract: PURPOSE: To evaluate the efficacy of intravitreal injections of two different dosages of bevacizumab (Avastin) for treating diffuse diabetic macular edema. METHODS: Fifty-two eyes of 52 patients with diabetic macular edema were randomized to receive three monthly intravitreal injections of 1.25 mg or 2.5 mg bevacizumab. Patients were observed for 6 months and optical coherence tomography central foveal thickness, logMAR best-corrected visual acuity (BCVA), and adverse events were assessed. RESULTS: Forty-eight eyes of 48 patients completed the 6-month follow-up and were analyzed. Significant mean central foveal thickness reductions were observed in both groups at all follow-up visits (P < 0.013). Significant improvements between baseline and 6-month mean logMAR BCVAs were seen, with the mean logMAR BCVA improved from 0.63 to 0.52 in the 1.25 mg group and 0.60 to 0.47 in the 2.5 mg group. No significant difference in BCVA was observed between the two groups at any time point (P > 0.56). Subgroup analysis showed that intravitreal bevacizumab seemed to be more effective in eyes without any previous diabetic macular edema treatment. CONCLUSIONS: Three monthly intravitreal bevacizumab injections resulted in significant reduction in central foveal thickness and improvements in BCVA in diabetic macular edema patients. Both 1.25 mg and 2.5 mg seemed to have similar treatment efficacy.

Chan CK, Lin SG. · Southern California Desert Retina Consultants, Palm Springs, CA 92263, USA. · Eur J Ophthalmol. · Pubmed #17671950 No free full text.

Abstract: PURPOSE: To describe the unusual complication of retinal pigment epithelial (RPE) tear after intravitreal ranibizumab (Lucentis) for subfoveal fibrovascular pigment epithelial detachment (PED) and its effective management. METHODS: Chart review for case report of RPE tear after ranibizumab. RESULTS: An inferior RPE tear was documented by fluorescein angiography, fundus photography, and optical coherence tomography (OCT) 1 month after receiving repeat ranibizumab injection in the right eye of a patient with bilateral subfoveal fibrovascular PED. He had undergone multiple bevacizumab followed by ranibizumab injections for neovascular age-related macular degeneration (AMD) in both eyes, starting 6 months previously. Subsequent antivascular endothelial growth factor (VEGF) therapy improved vision of right eye from 20/200 to 20/40, despite RPE tear. CONCLUSIONS: RPE tear may form after anti-VEGF therapy, including ranibizumab injection. Further anti-VEGF therapy may preserve or improve vision. To the authors' knowledge, this is first case report of effective suppression of neovascular activity with bevacizumab after an RPE tear following ranibizumab therapy.

Chan CK, Meyer CH, Gross JG, Abraham P, Nuthi AS, Kokame GT, Lin SG, Rauser ME, Kaiser PK. · Southern California Desert Retina Consultants, Palm Springs, CA 92263, USA. · Retina. · Pubmed #17558314 No free full text.

Abstract: 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 mm vs 9.9 mm, 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.

Lam DS, Chan CK, Mohamed S, Lai TY, Lee VY, Liu DT, Li KK, Li PS, Shanmugam MP. · Department of Ophthalmology and Visual Sciences, Chinese University of Hong Kong, Hong Kong, China. · Ophthalmology. · Pubmed #17459479 No free full text.

Abstract: OBJECTIVE: To evaluate the efficacy of sequential intravitreal triamcinolone acetonide (TA) injection followed by grid laser photocoagulation for treating diabetic macular edema (DME). DESIGN: Prospective, 3-armed, randomized clinical trial. PARTICIPANTS: One hundred eleven eyes of 111 patients with DME involving the fovea. INTERVENTION: Patients were randomized to grid laser photocoagulation (37 eyes), 4 mg of intravitreal TA (38 eyes), or 4 mg of intravitreal TA combined with sequential grid laser about 1 month later (36 eyes). MAIN OUTCOME MEASURES: Central foveal thickness (CFT) as measured by optical coherence tomography, logarithm of the minimum angle of resolution (logMAR) best-corrected visual acuity (BCVA), and side effect profiles. The 6-month results are reported. RESULTS: All patients completed 6 months' follow-up. Baseline mean (+/- standard deviation) CFTs were 385+/-100 microm, 396+/-91 microm, and 424+/-108 microm for the laser, intravitreal TA, and combined groups, respectively (P = 0.24). After treatment, significant CFT reductions were noted in both the intravitreal TA and combined groups at all follow-up visits (P<0.01) but not in the laser group. Mean CFT improved significantly to minimums of 267+/-75 microm and 256+/-73 microm for the intravitreal TA and combined groups, respectively, but the difference between the 3 groups was not significant at 6 months. The standardized change in macular thickening at 17 weeks was significantly greater in the combined group versus the intravitreal TA group (P = 0.007), suggesting that combined treatment might prolong the effects of intravitreal TA. Mean baseline logMAR BCVAs were 0.64+/-0.37, 0.72+/-0.34, and 0.69+/-0.34 in the laser, intravitreal TA, and combined groups, respectively (P = 0.67). Best-corrected visual acuity improved significantly at 4 and 9 weeks for the intravitreal TA group but did not change significantly in the other 2 groups. No significant difference in BCVA was observed between the 3 groups at any time point. CONCLUSIONS: Contrary to the results of a recent study, combined treatment of intravitreal TA plus grid laser did not yield better CFT reduction or BCVA improvement at 6 months than intravitreal TA alone. Grid laser alone was significantly worse than the 2 other treatment modalities.

Lam DS, Chan CK, Mohamed S, Lai TY, Li KK, Li PS, Tsang CW, Chan WM, Shanmugam MP. · Department of Ophthalmology & Visual Sciences, The Chinese University of Hong Kong, Hong Kong. · Br J Ophthalmol. · Pubmed #16973659 No free full text.

Abstract: OBJECTIVE: To compare the safety and efficacy of different doses of intravitreal triamcinolone (ivTA) in treating clinically significant diabetic macular oedema (CSMO). METHODS: 63 eyes of 63 patients with CSMO and central foveal thickness (CFT) of > or =250 microm on optical coherence tomography were randomised to receive 4 mg (n = 23), 6 mg (n = 20) or 8 mg (n = 20) ivTA. Patients were followed up for 6 months, and changes in best-corrected visual acuity (BCVA), optical coherence tomography CFT, standardised change in macular thickness (SCMT), and side effects such as intraocular pressure and cataractogenesis were compared between the three groups. RESULTS: After ivTA injection, improvements of BCVA and CFT occurred in all groups. The mean BCVA improvement at 6 months was significantly higher for the 8 mg group compared with the 4 mg group, with 9.9 and 3.1 improvement in letters on the Early Treatment of Diabetic Retinopathy Study chart, respectively (p = 0.047). The mean SCMT at 6 months for the 4, 6 and 8 mg groups was 28.7%, 42.3% and 60.5%, respectively (p = 0.06). The proportion of eyes with SCMT > or =75% at 6 months was higher in the 8 mg group, but the difference failed to reach significance (p = 0.06). Ocular hypertensive responses (>21 mm Hg) occurred in 39%, 30% and 55% of eyes in the 4, 6, and 8 mg groups, respectively (p = 0.27). CONCLUSIONS: Higher doses of ivTA may prolong the duration of visual benefit in diabetic CSMO and seemed to result in more sustained reduction in macular oedema. Further studies are warranted to investigate the optimum dose of ivTA in treating diabetic CSMO.

Chan CK, Mohamed S, Shanmugam MP, Tsang CW, Lai TY, Lam DS. · Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, University Eye Center, Hong Kong Eye Hospital, 147K, Argyle Street, Hong Kong. · Br J Ophthalmol. · Pubmed #16707525 No free full text.

Abstract: BACKGROUND/AIM: Intravitreal triamcinolone (IVTA) results in transient improvements in diabetic macular oedema (DMO), necessitating repeated injections. The authors report a case series of 10 eyes of 10 patients with DMO, who received a repeat injection of 4 mg IVTA, at least 26 weeks after the first injection of the same dose. METHOD: Pre-injection and at 2, 4, 9, and 17 weeks post-injection, best corrected visual acuity (BCVA) and central foveal thickness (CFT) on optical coherence tomography, after the first and repeat injections, were compared using paired t test. Side effects were monitored. RESULTS: BCVA, CFT, intraocular pressure (IOP), and cataract scores were not significantly different before initial and repeat injections (given at 32.5 (SD 3.5) weeks after the first injection). Transient improvements of BCVA and CFT were achieved after both injections. However, after the repeat injection, the BCVA was significantly worse at all time points (p<0.05) and so were the best achieved CFT and the CFT at 4 weeks post-injection (p = 0.034 and 0.011 respectively), compared with the initial injection. Post-injection maximum IOPs and increase in cataract scores were not significantly different between the two injections. CONCLUSION: A repeat injection of 4 mg of IVTA may not be as effective as an initial injection for the treatment of DMO.

Lam DS, Chan CK, Tang EW, Li KK, Fan DS, Chan WM. · Department of Ophthalmology and Visual Sciences, Chinese University of Hong Kong, Hong Kong Eye Hospital, Hong Kong. · Clin Experiment Ophthalmol. · Pubmed #15575825 No free full text.

Abstract: AIM: To evaluate the safety and efficacy of intravitreal triamcinolone (IVTA) in Chinese patients with diabetic clinical significant macular oedema (CSMO). METHODS: Eighteen eyes of 17 consecutive patients with CSMO were prospectively recruited and treated with a 4 mg injection of IVTA. Best-corrected visual acuity (BCVA) on the ETDRS chart and central macular thickness (CMT) on optical coherence tomography were measured at baseline weeks 1, 2, 3, and months 1, 2, 3, 4, 5 and 6. Side-effects were monitored. RESULTS: All patients completed 6 months of follow up. The mean baseline BCVA and CMT were 1.20 +/- 0.31 logMAR units and 552 +/- 179 microm, respectively. Improvements in CMT and BCVA were observed as early as at 1 and 2 weeks, respectively (P < 0.05). Mean BCVA peaked at 2 months (0.97 +/- 0.38 logMAR units) while mean CMT was maximally reduced at 3 months (326 +/- 145 microm). Improvements in BCVA and CMT were less afterwards but still statistically significant at 6 months; the final mean BCVA and CMT were 0.99 +/- 0.36 logMAR units and 427 +/- 145 microm, respectively. A total of 5/18 (28%) eyes developed a transient increase in intraocular pressure. Cataract progression was noted in 2/12 (17%) of the phakic eyes. CONCLUSIONS: Intravitreal triamcinolone appeared generally safe and effective in Chinese patients with CSMO. Although the improvements in BCVA and CMT were transient, there were residual benefits at 6 months. Due to the transient nature of IVTA, re-treatment seems necessary but the optimal timing and dosage will require further investigations.

Lam DS, Chan CK, Mohamed S, Lai TY, Lee VY, Lai WW, Fan DS, Chan WM. · Department of Ophthalmology & Visual Sciences, The Chinese University of Hong Kong, Hong Kong Eye Hospital, Hong Kong. · Eye. · Pubmed #15389275 No free full text.

Abstract: AIMS: To assess the safety and efficacy of phacoemulsification with intravitreal triamcinolone (ivTA) injection in diabetics with cataract and clinically significant macular oedema (CSMO). METHODS: A total of 19 eyes of 15 consecutive diabetic patients with cataract and CSMO were prospectively recruited. Patients underwent phacoemulsification and intraocular lens implantation with 4 mg ivTA injection at completion of surgery. Patients were followed up on day 1, then weekly for 1 month, and thereafter monthly until 6 months postoperatively. Best corrected visual acuity (BCVA), central macular thickness (CMT) measured by optical coherence tomography, and adverse events were recorded. RESULTS: In total, 17 eyes completed 6 months of follow-up. In all, 58.8% showed improvement in BCVA of >or=2 lines, with statistically significant improvement in mean Snellen BCVA of 2.4 lines at 6 months. The peak BCVA was achieved at 4 months. The mean CMT decreased from a baseline of 449 microm to a minimum of 321+/-148 microm (28.5% reduction) achieved at 2 months, with statistically significant reduction at all postoperative time intervals until 6 months. Of 17 eyes, 4 (23.5%) developed transiently elevated intraocular pressure that normalised by 6 months in all but one patient. No injection- or surgery-related complications were encountered. CONCLUSIONS: Phacoemulsification with concurrent 4 mg ivTA injection appears to be a safe option for managing diabetics with cataract and CSMO. However, large-scaled randomised controlled trials are necessary for delineating the relative contributions of cataract removal and CMT reduction to visual improvement. Moreover, the transient effect on CMT may warrant further studies to determine optimal timing and dosage of further ivTA injections.

Chan CK, Chan WM, Cheung BT, Yuen CY, Lee VY, Lam DS. · No affiliation provided · Arch Ophthalmol. · Pubmed #15249387 No free full text.

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