THE LATEST RESEARCH

Exploring Infliximab as a Treatment for Uveitis
Two studies of infliximab (Remicade, Centocor) for the treatment of refractory autoimmune uveitis were recently published. The intravenously infused drug acts against tumor necrosis factor alpha and is Food and Drug Administration-approved for the treatment of Crohn’s disease and rheumatoid arthritis.

In a Phase II, prospective, open-label study conducted at the Casey Eye Institute in Portland, Ore., the treatment benefited some patients, but the incidence of serious adverse events was unexpectedly high. Doctors enrolled 23 patients, who received infliximab infusions at baseline, week two and week six. The 18 patients who met the criteria for success at week 10 received infusions at week 14 and every eight weeks thereafter until week 50. Seven of 14 patients enrolled for one year continued infliximab therapy and maintained their successful grading. Five did not complete one year of treatment because of significant adverse events possibly related to infliximab, including pulmonary embolus, congestive heart failure, lupus-like reaction and vitreous hemorrhage. Fifteen of 20 patients who received three or more infusions developed anti-nuclear antibodies.

Another study, conducted at Istanbul University in Turkey, involved 13 male patients with Behçet’s disease and uveitis resistant to combination therapy with corticosteroids, azathioprine, and cyclosporine. They had experienced 32 uveitis attacks involving the posterior segment. They received infliximab infusions (5 mg/kg) at baseline and weeks two, six and 14 of the study. During the infusion period through week 22, four patients experienced no uveitis attacks and nine patients had a total of 13 attacks. During weeks 23 to 54, one patient remained in remission and the remaining 12 patients had a total of 36 uveitis attacks. The mean number of uveitis attacks and daily corticosteroid doses were significantly lower during the infusion period than during the previous-treatment period or the observation period. Improved visual acuity was not sustained to week 54. No serious adverse events occurred.

Sources: Suhler EB, Smith JR, Wertheim MS, et al. A prospective trial of infliximab therapy for refractory uveitis: preliminary safety and efficacy outcomes. Arch Ophthalmol 2005;123:903-12. Tugal-Tutkun I, Mudun A, Urgancioglu M, et al. Efficacy of infliximab in the treatment of uveitis that is resistant to treatment with the combination of azathioprine, cyclosporine, and corticosteroids in Behcet’s disease: an open-label trial. Arthritis Rheum 2005;52(8):2478-84.

Study Shows Higher Doses of Triamcinolone Produce Better Results in Patients with Diffuse DME
Researchers in Germany compared three different doses of triamcinolone acetonide in 27 eyes of patients with diffuse diabetic macular edema and concluded that treatment response may last longer and be more pronounced with a 13-mg dose than with doses of 5 mg or 2 mg. They also found that intraocular pressure was not significantly associated with dosage. In their prospective, randomized, double-masked study, eight eyes received a 2-mg dose, 10 eyes received a 5-mg dose, and nine eyes received a 13-mg dose. Mean follow-up was 6.6 months with a range of three to 12 months. Maximal increase in visual acuity correlated significantly with dosage level (p=0.046), and duration of effect increased significantly with dosage level (p=0.014). Also, increase in intraocular pressure during follow-up was not significantly associated with dosage (p=0.77).

Source: Spandau UHM, Derse M, Schmitz-Valckenberg P, et al. Dosage dependency of intravitreal triamcinolone acetonide as treatment for diabetic macular oedema. Br J Ophthalmol 2005;89:999-1003.

Incidence of Acute Endophthalmitis Following Intravitreal Triamcinolone Injection
In a retrospective, noncomparative, consecutive, interventional case series of all 1,006 eyes that received an in-office intravitreal injection of triamcinolone acetonide at two clinical centers between Jan.1, 2000 and Jan. 30, 2004, the incidence of acute endophthalmitis was 0.10 percent. None of the eyes developed culture-positive endophthalmitis in the six weeks after injection. One eye developed culture-negative endophthalmitis four days after injection. In that case, the patient experienced decreased vision but no pain. Acute conjunctival erythema but no hypopyon was observed.

Source: Westfall AC, Osborn A, Kuhl D, et al. Acute endophthalmitis incidence intravitreal triamcinolone. Arch Ophthalmol 2005;123:1075-77.

MORE FROM THIS SUMMER’S ANNUAL MEETING OF THE AMERICAN SOCIETY OF RETINA SPECIALISTS

Complications of Intravitreal Triamcinolone in 1,000 Eyes
Ocular hypertension, culture-negative endophthalmitis, intraocular inflammation, and cataract progression were among the complications noted in a retrospective review of 1,000 eyes treated for various macular conditions with either 2 mg or 4 mg of triamcinolone acetonide. The review included 1,594 injections over 36 months; mean follow-up was 8.5 months. Complications and their rates of occurrence were: ocular hypertension >21 mmHg (38.4 percent); ocular hypertension >28 mmHg (13.5 percent); cataract progression (18.4 percent); cataract extraction (7.4 percent); culture-negative endophthalmitis (five eyes, 0.3 percent); moderate intraocular inflammation (four eyes, 0.25 percent). One eye (0.06 percent) developed a central retinal vein occlusion three months after injection. At six months, 25.2 percent of eyes gained two or more lines of Snellen visual acuity, 40.1 percent remained the same, and 34.7 percent lost two or more lines.

Source: Complications associated with intravitreal triamcinolone acetonide injection -- a study of 1,000 eyes, Roth DB, Heimmel M, Gloth J, et al., 2005 ASRS scientific paper presentation, Montreal, Quebec, Canada.

Acute Triamcinolone Injection for Retinal Vein Occlusions
According to the results of a recent study, acute injection of triamcinolone acetonide for ischemic and non-ischemic retinal vein occlusions may result in faster and more significant improvement in visual acuity and cystoid macular edema (CME) than conventional management. Records of 13 consecutive eyes were reviewed. Nine eyes had central retinal vein occlusions (CRVO); two eyes had hemiretinal vein occlusions (HRVO); and two eyes had branch retinal vein occlusions (BRVO). All eyes received a 4-mg injection of triamcinolone within one month of the onset of decreased vision. Mean follow-up was 6.8 months.

In all types of occlusions, mean visual acuity improved significantly (p < 0.005) from pre-injection to most recent follow-up visit (20/182 to 20/58 in CRVO, 20/448 to 20/45 in HRVO, and 20/142 to 20/49 in BRVO). CME resolved or was reduced in all 13 eyes. Mean central foveal thickness as measured by optical coherence tomography was reduced from 634 µm pre-injection to 257 µm post-injection. Three eyes were reinjected for refractory or recurrent CME. Elevated intraocular pressure requiring short-term medical treatment occurred in one eye.

Source: Acute intravitreal triamcinolone injection for retinal vein occlusion, Hassan TS, Williams GA, Capone A, et al., 2005 ASRS scientific paper presentation, Montreal, Quebec, Canada.

Verteporfin PDT and Lesions with Retinal Anastomosis
The Verteporfin in Photodynamic Therapy (VIP) Study Group reported that the presence of a retinal anastomosis in occult with no classic CNV appears to have no effect on the visual acuity outcomes of the treatment. The research group reviewed baseline stereoscopic color photographs and fluorescein angiograms of patients who received either verteporfin therapy or placebo with sham treatment in the VIP trial. Seventeen (10 percent) of 166 verteporfin-treated patients with occult with no classic CNV had anastomoses at baseline compared with 10 (11 percent) of 92 placebo recipients. The anastomoses did not influence mean visual acuity change from baseline, percentage of eyes with at least a three- or six-line loss from baseline, or percentage of eyes with visual acuity of 20/200 or worse. Therefore, the researchers concluded that the presence or absence of an anastomosis on fluorescein angiography should not influence verteporfin therapy treatment recommendations.

Source: Retinal anastomosis to the lesion (RAL), aka "RAP," in occult with no classic CNV: impact on verteporfin therapy, Bressler SB, Bressler NM, Solomon SD, VIP Study Group, 2005 ASRS scientific paper presentation, Montreal, Quebec, Canada.

The 23-ga. surgery system developed by Dutch Ophthalmic Research Center.

Evaluation of 23-Ga. Vitrectomy
Surgeons who conducted a retrospective review of 33 consecutive 23-ga. sutureless transconjunctival pars plana vitrectomies reported that the technique combines the benefits of minimally invasive transconjunctival surgery without some of the limitations of 25-ga. surgery and allows sutureless procedures to be performed in more complex cases. No intraoperative complications occurred. Only two sclerotomies required suturing, and mean intraocular pressure one day after surgery was 21 mmHg.

They also reported that the 23-ga. instruments were sturdier and more versatile than 25-ga. instruments, but that 23-ga. trocars were more difficult to place and often caused a small subconjunctival hemorrhage when removed. Wound closure for 23-ga. sclerotomies was superior to 25-ga. sclerotomies in the study. The surgeons performed the vitrectomies for several different conditions, using a system developed by Dutch Ophthalmic Research Center.

Source: 23-gauge sutureless transconjunctival vitrectomy, Iranmanesh R, Spaide RF, Fernandez CF, et al., 2005 ASRS scientific paper presentation, Montreal, Quebec, Canada.

Initial Surgeon Experience with 25-Ga. Vitrectomy
A retrospective review of one surgeon’s first 110 vitrectomies using a 25-ga. system (Alcon) over a six-month period provided information on advantages and disadvantages of the technique and possible complications. Cases were selected for 25-ga. surgery based on the feasibility of accomplishing the surgical objectives with smaller instruments, fewer accessory instruments and reduced illumination. Mean time to recovery of final visual acuity showed a trend toward shorter recovery. Patient discomfort, external ocular irritation and conjunctival ecchymosis and chemosis were significantly reduced. Complications included subconjunctival gas in five eyes, air/gas in anterior chamber in six eyes, which caused anterior subcapsular cataract in two eyes, retinal detachment in six eyes, vitrector breakage in two cases, and iris prolapse through clear corneal incision in two eyes.

No wound leaks, endophthalmitis or chronic hypotony requiring subsequent intervention occurred. Conversion to 20-ga. instrumentation was required in six eyes, and five eyes required intraoperative closure of sclerotomies.

Source: Advantages, disadvantages and complications converting to 25-gauge vitrectomy – first 110 cases, Thomas EL, Rudometkin NJ, 2005 ASRS scientific paper presentation, Montreal, Quebec, Canada.