Laird Harrison

July 20, 2015

VIENNA — Adding topical squalamine to ranibizumab (Lucentis, Genentech, Inc) improves visual acuity significantly more than ranibizumab alone in patients with retinal vein occlusion, a small trial shows.

"At week 10, I was already seeing better results than most trials at 1 year," said John Wroblewski, MD, from Cumberland Valley Retina Consultants, in Hagerstown, Maryland.

Dr Wroblewski presented the study results here at the American Society of Retina Specialists (ASRS) 2015 Annual Meeting.

The widely used macular edema drugs act only on vascular endothelial growth factor (VEGF); in contrast, squalamine inhibits platelet-derived growth factor, basic fibrous growth factor, and VEGF receptors 1 and 2, he told Medscape Medical News.

In addition, squalamine, which can be administered as an eye drop, permeates the sclera into the choroid. Ohr Pharmaceuticals has formulated the drug for this purpose, he reported.

In the study, Dr Wroblewski and his team tested the effectiveness of topical squalamine in retinal vein occlusion. The pair recruited 20 people who had not previously been treated for retinal vein occlusion. All had a central subfield thickness greater than 300 µm and best corrected visual acuity of 20/40 to 20/320.

All patients received squalamine eye drops for 10 weeks. Starting at week 2, they also received intravitreal ranibizumab 0.5 mg every 4 weeks.

The 19 patients classified as early treatment responders at 10 weeks did not require a third ranibizumab injection. Of these patients, 80% gained at least three lines of best corrected visual acuity.

After 10 weeks, 10 patients were randomly assigned to continue with the squalamine eye drops; the other 10 did not continue. All 20 patients continued taking ranibizumab as needed until the end of the study at week 38, depending on visual acuity and spectral domain optical coherence tomography.

At week 38, the improvement in visual acuity was better in patients who continued on squalamine than in those who did not, the reduction in macular volume was greater, and the number of injections needed was reduced.

Table. Outcomes With Squalamine

Outcome Continuous Squalamine Discontinuous Squalamine
Week 10 to Week 38    
Mean change in visual acuity, letters +7.4 +3.1
Gain of any letters, % 80 50
Loss of any letters, % 0 50
Reduction in total macular volume, % 20 0
Mean number of injections 2 3.3
Week 38    
Change from baseline in visual acuity, letters +27.8 +23.3
Central subfield thickness, µ 264 283


The results compared favorably with those of previous trials of VEGF inhibitors for retinal vein occlusion.

In the BRAVO, CRUISE, and SHORE trials, patients gained an average of 14.9 to 19.3 letters and lost an average of 2.8 to 3.3 letters of best corrected visual acuity 2 months after receiving the sixth or seventh injection.

In the current study, patients who discontinued squalamine lost 5.2 letters 2 months after their second injection, but those who continued squalamine lost only 0.4 letters.

Squalamine was well tolerated, and there were no ocular or systemic safety issues, said Dr Wroblewski.

Small studies like this raise as many or more questions than they answer. Dr Antonio Capone

Dr Wroblewski acknowledged that there were some limitations; the study was very small, took place at a single site, and had no control group. In addition, patients were not randomly assigned until week 10.

Still, the fact that squalamine appeared to strongly affect visual acuity without a proportionate effect on macular edema or the number of injections suggests that the study population was not particularly skewed toward people who respond well to ranibizumab, he explained.

These results warrant a phase 3 trial of squalamine as an adjunctive therapy for retinal vein occlusion. The drug might also have potential in some types of macular degeneration, he said.

"Small studies like this raise as many or more questions than they answer," said session monitor Antonio Capone, MD, from Associated Retinal Consultants, in Royal Oak, Michigan.

One of these questions is how long squalamine should be continued, he told Medscape Medical News.

Squalamine would likely be continued as long as the intravitreal injections, Dr Wroblewski said.

Dr Wroblewski reports that he is a consultant, on the medical advisory board, and a stockholder in Ohr Pharmaceuticals and is a consultant and on the advisory board for Allergan Pharmaceuticals. Dr Capone reports that he is a consultant for Allergan and Genentech.

American Society of Retina Specialists (ASRS) 2015 Annual Meeting. Presented July 11, 2015.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.