Topical Anti-VEGF Eye Drops
Squalamine Ophthalmic Solution as Topical Anti-VEGF Eye Drops
Squalamine is a small anti-angiogenic aminosterol molecule that inhibits multiple growth factors such as basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF).
Platelet-derived growth factor is known to be significantly elevated in patients with Central Retinal Vein Occlusions and basic fibroblast growth factor is known to be significantly elevated in patients with Branch Retinal Vein Occlusions.
These growth factors are responsible for the development of neovascularization (Abnormal new proliferating blood vessels due to pathological causes) inside the eye in patients with diabetic retinopathy, Retinal vein occlusions and Wet Age-Related Macular degeneration.
Squalamine also has potent antimicrobial activity against gram negative and gram positive bacteria, protozoa fungi and many viruses and it is discovered in the tissues of the dogfish.
Squalamine is positively charged molecule and it binds negatively charged phospholipids molecules of membrane such as that on the bacteria.
Combination of topical Squalamine 0.2% Ophthalmic Solution (OHR-102) with Anti-VEGF injections such as ranibizumab showed improvement in visual acuity in patients with choroidal neovascularization in Wet Age Related Macular Degeneration. These patients gained more than three lines on the ETDRS chart at nine months.
On Optical coherence tomography or OCT, Physiological improvements were seen such as improvement of central retinal thickness due to resolution of intraretinal and subretinal fluid and improvement of subretinal hyperreflective materials.
In one study, patients who discontinued squalamine and lost more than 5 letters 2 months after last injection, but those who continued squalamine lost only 0.4 letters.
Topical Squalamine 0.2% Ophthalmic Solution twice daily can penetrate the sclera into the choroid. It can improve visual acuities in choroidal neovascularization in a safe and non-invasive effective way with no ocular or systemic side effects but it can’t be used as monotherapy and it did not result in a decrease in the number of intravitreal injections of Anti-VEGF.
However, on 2018, the researchers were disappointed at the results of MAKO study. In this study, subjects who used Squalamine Eye Drops twice a day in combination with monthly injection of Ranibizumab were compared with subjects who received only monthly Ranibizumab on the means of visual acuity. Subjects who used combination of Squalamine Eye Drops and Ranibizumab gained only 8.33 letters compared to 10.58 letters with Ranibizumab monotherapy, thus this trail failed the primary goal of improving visual acuity