ICO in Sydney draws attendees from around the world

The meeting demonstrated the diversity of global ophthalmology.

SYDNEY — The breadth and diversity of worldwide ophthalmology was on display here at the 29th International Congress of Ophthalmology.

The meeting attracted a total of 4,500 medical and industry participants from all over the world. On the podium, drugs in development for retinal disease and glaucoma shared the podium with traditional Chinese herbal medicines that have been in use for 1,500 years. Other discussions highlighted the differences in glaucoma’s manifestations in different parts of the world. And surgeons from every continent presented new ideas on iris color’s effect on glaucoma surgery, pregnancy and glaucoma, and a wide range of other topics.

This article recaps a few of the highlights of the Sydney meeting. The next meeting of the ICO, which is held every 4 years, will be in São Paulo in 2006.

Pharmacology for diabetic retinopathy

Improved understanding of the pathways involved in diabetes-induced microvascular damage has led to innovative emerging pharmacological therapies for the treatment of diabetic retinopathy and diabetic macular edema, according to Anselm Kampik, MD, of Munich.

Nearly 5,000 people attended the ICO meeting in Sydney.

Dr. Kampik, who spoke during a symposium on Emerging Issues in the Diagnosis and Treatment of Diabetic Retinopathy and Diabetic Macular Edema, said results from phase 3 trials of aminoguanidine have shown beneficial effects on the progression of retinopathy, although an increase in anemia was associated with the drug’s use.

Other potential treatments under investigation in multicenter trials include a sorbitol inhibitor, calcium dobesilate; an antioxidant, alphalipoic acid; a somatostatin analogue, octreotide; an angiotensin receptor blocker, candesartan; and a protein kinase C (PKC)-beta inhibitor.

According to Dr. Kampik, recent reports indicate that the PKC-beta isoform inhibitor can improve retinal blood flow abnormalities in patients with Type 1 or Type 2 diabetes. Phase 3 trials for the PKC-beta inhibitor are under way to determine whether it has any beneficial effects on the progression of diabetic retinopathy or diabetic macular edema, he said.

Anti-VEGF therapy for AMD

Anti-angiogenic agents offer the potential for treating exudative age-related macular degeneration (AMD), said David Guyer, MD, of New York.

“Anti-VEGF therapy appears to be where the action is,” he said. “If you inject VEGF, you get neovascularization. Anti-VEGF will prevent neovascularization.”

Dr. Guyer reported results of anti-vascular endothelial growth factor (anti-VEGF) therapy here. Intravitreal injections of anti-VEGF therapy were performed in 36 patients with choroidal neovascularization (CNV). No drug-related serious adverse events were noted, he said. Eighty percent of patients exhibited stable or improved vision at 3 months post-injection. Also, 20% of patients with subfoveal CNV in AMD showed an improvement of 3 or more lines at 3 months.

Chinese herbs and geographic atrophy

From the other side of the world, Lycium barbarum may help patients who suffer from geographic atrophy, a form of dry age-related macular degeneration. Lycium barbarum has been in the Chinese pharmacopoeia for the promotion of good vision since A.D. 500.

Geographic atrophy is a progressive, blinding disease resulting in atrophy of the photoreceptor cells, pigment epithelium and choroid capillaries, eventually leading to vision loss. Age-related macular degeneration is one of the major causes of blindness in the western world, according to Mark O.M. Tso, MD, of Baltimore.

Lycium barbarum contains more zeaxanthin than any other fruit or vegetable, Dr. Tso said. Just one of these Chinese berries contains 300 mg of zeaxanthin, an antioxidant that is believed to protect the macula by filtering out harmful blue light.

Zeaxanthin is the dominant carotenoid present in the macula. Another carotenoid, lutein, is mostly present in the retina peripherally. However, neither of these pigments can be synthesized in the human body; they have to be provided via dietary intake.

According to Dr. Tso, a clinical trial for patients with geographic atrophy but without subretinal pigment epithelial neovascularization is being conducted. Dr. Tso hopes that Lycium barbarum may be able to provide the macular cells with zeaxanthin and retard the progression of geographic atrophy.

Glaucoma combo drugs

Xalacom once daily was more effective for the reduction of IOP than Cosopt twice daily in patients with primary open-angle glaucoma or ocular hypertension, according to a study presented here in poster form by Robert M. Feldman, MD, of Altamonte Springs, Fla.

The primary objective of the study was to measure the difference in diurnal mean IOP reduction between a fixed combination of latanoprost and timolol (Xalacom, Pharmacia, known in the United States as Xalcom) and a fixed combination of dorzolamide and timolol (Cosopt, Merck) in patients with elevated IOP.

In 30 U.S. eye centers, 249 patients with primary open-angle glaucoma or ocular hypertension were enrolled in a randomized, parallel, investigator-masked, multicenter comparison trial.

After 3 months of therapy, mean diurnal IOP reduction from baseline was 9.4 ± 0.27 mm Hg for Xalacom and 8.4 ± 0.26 mm Hg for Cosopt. Xalcom recorded a difference in mean IOP reduction of 1 mm Hg more than Cosopt, the study authors said.

Although both drugs were well tolerated and adverse events were similar, three times as many patients who received Cosopt reported eye pain, according to the poster. Additionally, eyes treated with Cosopt had more reported eye irritation than eyes treated with Xalacom.

Endothelin-1 levels in glaucoma

Elevated endothelin-1 levels have been found in the blood of patients with primary open-angle glaucoma but they may not be responsible for the condition, according to one researcher.

Endothelin-1 is “not just a bad guy you want to shoot down,” according to Selim Argul, MD, of Switzerland, who discussed endothelin-1 (ET-1) and its effects on glaucoma here. ET-1 does, however, need to be understood and controlled, he added.

Dr. Argul said slightly increased levels of ET-1 may increase ocular tissue’s sensitivity to other vasoconstrictors, causing vascular dysregulation and disturbed autoregulation. The cause of this increase is unclear, he said.

Dr. Argul said increased levels of ET-1 may not per se explain glaucomatous damage. Studies are under way, he said, that may show glaucoma-like damage of the optic nerve head can be caused by elevated levels of ET-1, with or without high levels of IOP.

He said that although further studies are warranted, agents such as unoprostone, which have been shown to reduce the vasoconstriction caused by ET-1, may be effective in treating its effects.

Primary angle-closure glaucoma

In the region of the world where the ICO took place, primary angle-closure glaucoma is a “huge” problem, said Harry Quigley, MD, of Baltimore.

An estimated 7.6 million people are bilaterally blind from glaucoma, almost the same number as from trachoma, according to Dr. Quigley. Because the morbidity of primary angle-closure glaucoma is twice that of open-angle glaucoma, he said, in 4.3 million of those blind from glaucoma the cause is primary angle-closure glaucoma. Open-angle glaucoma is much more common than primary angle-closure glaucoma among European, African and Hispanic people, but primary angle-closure glaucoma is more prevalent among Chinese, South Asian and Indian populations. Primary angle-closure glaucoma is three times more prevalent among women than men, he added.

According to Dr. Quigley, physiological responses within the choroid and vitreous are among the reasons for these differences, because the proportions of those with small eye dimensions are similar across world populations.

Long-term latanoprost

Long-term use of latanoprost for the treatment of glaucoma is not associated with serious adverse events and is helpful in sustaining IOP reduction, according to a poster presentation.

Albert Alm, MD, of Uppsala, Sweden, and colleagues conducted a multicenter study in Sweden, Great Britain, the Netherlands, Australia and Belgium, in which 519 patients with uncontrolled unilateral or bilateral open-angle glaucoma or exfoliation glaucoma were enrolled in a 3-year open-label study.

In three 6-month phase 3 trials with latanoprost, the most commonly reported adverse events included blurred vision, burning, stinging, conjunctival hyperemia, foreign body sensation, itching and ocular discomfort. Clinically significant side effects during a 2-year experience consisted of an increase in iris pigmentation.

Patients instilled latanoprost 0.005% once daily in the evening as adjunctive treatment; 87% of patients were taking beta-blockers at the start of the study.

At the beginning of the 2-year extension study, 88% of 380 patients were treated in both eyes with latanoprost. Follow-up was quarterly until month 48, then follow-up was every 6 months. Increased pigmentation occurred in 33% of 380 patients. Onset of the increase in pigmentation occurred during the first 8 months of the study for most of these patients (74%).

During 5-year follow-up, 72% of patients’ IOPs were well controlled without treatment modification or surgery.

During a 3-year study, five cases of iritis/anterior uveitis were reported in latanoprost-treated eyes and one case in an untreated eye.

Iris color and cyclophotoablation

A correlation exists between iris color and the degree to which the ciliary processes absorb laser energy in cyclophotoablation, according to a study by Ronit Nesher, MD, of Mevasseret Zion, Israel.

“Although further study is warranted, this information is valuable in the selection of treatment parameters and may also result in better treatment of glaucoma patients,” Dr. Nesher said.

She explained that cyclophotoablation is dependent on the amount of laser absorbed by the tissue, which is in turn related to the degree of iris pigmentation. However, she added that there are no set guidelines for laser power adjustment, and some patients require more than one procedure.

In the study, Dr. Nesher and colleagues studied histologic specimens from 31 enucleated eyes. The pigmented epithelium of the ciliary processes was qualitatively evaluated. Information on iris color was received via telephone interviews for 22 eyes. In the remaining nine eyes, iris color was defined from wet tissue. Nineteen eyes had brown irides (group A), and 12 eyes had light-colored irides (group B).

Group A had a greater incidence of cell pigmentation, blurring of cell margins, number and aggregation of melanosomes and ciliary vascularization than those in group B, and a reduced number of vacuoles compared to group B.

Pregnancy and glaucoma

Retinal blood flow does not decrease during pregnancy, according to a study presented by Magdalena Pilas-Pomykalska, MD, of Poland. She and colleagues attempted to define changes in capillary blood flow during normal pregnancy.

“During pregnancy, significant changes are observed in the maternal circulatory system. We questioned if pregnancy is or is not a risk factor for glaucoma progression due to hemodynamic changes in retinal microcirculation,” she said.

They followed seven healthy pregnant women throughout their pregnancies. Full ophthalmologic examinations were performed to rule out any eye diseases. Mean capillary blood flow of the peripapillary retinal region was measured with the Scanning Laser Doppler Flowmeter (Heidelberg Engineering).

Dr. Pilas-Pomykalska said an increase of retinal blood flow during the successive stages of pregnancy was observed in both eyes in each of the patients. Furthermore, there actually was an increase in capillary retinal blood flow with advancing gestation, she said.

Hepatitis in donor corneas

The accuracy of screening for hepatitis C virus in donor corneas is questionable, according to a report here.

“Many corneas are discarded unnecessarily,” said Uri Rehany, MD, of Nahariya, Israel. “We need to try to increase the use of the tissue that we have.”

Of donor corneas rejected for transplantation, the largest group comprises donors testing positive for hepatitis C virus (HCV), Dr. Rehany said. He said the prevalence of HCV in corneal donors can be more than 10% in many countries. He added, however, that the lack of correlation between HCV immunologic results and of evidence for HCV RNA in the serum and donor corneal tissue raises questions regarding the value of the donor HCV screening.

Dr. Rehany and colleagues tested for the HCV antigen by using immunology and polymerase chain reaction (PCR) studies in donor corneal tissue. Eight corneas of four seropositive corneal donors and eight corneas of 4 seronegative corneal donors were examined. Dr. Rehany found that HCV RNA was not detected in the donor corneal tissue with either PCR or immunohistochemical testing.

He noted that a larger study investigating the sensitivity, specificity and clinical applicability of the PCR and immunohistochemical method for the HCV antigen is warranted.

IOLs and uveitis

Excellent post-cataract outcomes are possible in patients with uveitis who have been implanted with hydrophilic acrylic IOLs, according to a study discussed here.

Vinod Kumar, MD, evaluated the Rayner 570H and 574H injectable acrylic posterior chamber IOLs, implanted following phacoemulsification in uveitic patients. He said studies have not yet determined the ideal foldable IOL for use in patients with uveitis.

Dr. Kumar and colleagues retrospectively reviewed the results of 570H and 574H IOL implantations in 21 consecutive eyes of 17 patients with various types of uveitis.

At a mean follow-up of 5.6 months, visual acuity had improved in all eyes compared with preoperative levels. Fourteen eyes had achieved 6/9 or better vision. Dr. Kumar said the main cause for reduced visual acuity was existing macular edema or scar.

Postoperatively, 95% of patients had visual improvement. Seventy-five percent of patients had 6/12 or better vision. If existing pathology is excluded, this figure went up to more than 90%, Dr. Kumar said.

No significant complications occurred in the study, and both IOLs appear safe to implant in uveitic patients. There were no cases of significant deposits on the IOLs, fibrinous uveitis or anterior capsular phimosis.

Cleanliness and endophthalmitis

Good surgical practices are of the utmost importance in the prevention of postoperative endophthalmitis, according to one presenter here.

Kensaku Miyake, MD, of Nagoya, Japan, said there are several points to keep in mind during cataract surgery. He said keeping the operating room as clean as possible, disinfecting the eyelid and conjunctiva with povidone iodine, having a secure drape, teaching proper hygiene habits to surgeons and staff and “performing a flawless operation” are all essential in preventing endophthalmitis.

In a retrospective study of about 40,000 eyes that underwent cataract surgery, when these measures were followed, Dr. Miyake said a “dramatic” reduction in postop infection was seen. The few infections that did develop were opportunistic infections associated with other conditions, such as diabetes or cancer, or they occurred in the late postoperative phase, he said.