Effects of Bisphosphonates on Choroidal Neovascularization
Effects of Bisphosphonates on Choroidal Neovascularization
Background Choroidal neovascularisation is often associated with pathological myopia. Bisphosphonates (BP), the preferred drug for treatment of osteoporosis, are known to have anti-angiogenic effects.
Objective To compare the therapeutic effects of oral BP with anti-vascular endothelial growth factor therapy (anti-VEGF) and photodynamic therapy (PDT) for myopic choroidal neovascularisation (mCNV) over 2 years of follow-up.
Methods One hundred eyes of 96 consecutive patients with mCNV who underwent oral BP treatment (alendronate 5 mg/day or 35 mg/week), anti-VEGF therapy, PDT or observation only were followed up for 2 years. The best-corrected visual acuity (BCVA) and the central retinal thickness (CRT) in optical coherence tomography were compared among the treatment groups.
Results The mean BCVA of the patients was maintained for up to 2 years in the BP and PDT groups. In the anti-VEGF group, the mean BCVA was significantly improved but was significantly worse in the no-treatment group. The visual outcomes were significantly better in the BP, PDT and anti-VEGF groups than the no-treatment group over 2 years of follow-up (−0.28, −0.26 and −0.39 logMAR units, p=0.032, 0.021 and 0.0004, respectively). The mean CRT was significantly decreased in all treatment groups (−84, −121 and −122 mm, p=0.0025, 0.017 and 0.000025, respectively).
Conclusions Oral BP should be investigated further as possible therapeutic and preventive drugs for mCNV.
Pathological myopia is the leading cause of choroidal neovascularisation (CNV) in people under 50 years old. Patients with pathological myopia are common in Asian populations, including the Japanese population, and the number of patients has increased over the years. Myopic choroidal neovascularisation (mCNV) is a major complication of pathological myopia, which has a poor prognosis in its natural course; the visual acuity decreases to less than 20/200 in 89% of the eyes after 5 years.
Recently, a number of studies have reported that intravitreal injections of recombinant humanised monoclonal antibodies against vascular endothelial growth factor (VEGF), such as bevacisumab or ranibizumab, are effective against mCNV. However, repeated injections of anti-VEGF agents are needed to keep the lesion stable and to maintain vision, with one report indicating that a mean of 2.5 injections of ranibizumab or 4.7 injections of bevacizumab were required over 18 months of follow-up. These re-treatments may pose a cumulative risk of ocular and systemic complications such as endophthalmitis and strokes, and are a burden for patients and healthcare systems. Hence, we were interested in finding alternative treatments using oral drugs or eye drops, which are usually less expensive, easier to use and may also be used for prevention.
Bisphosphonates (BP) are powerful inhibitors of osteoclasts, and are the preferred drug for treatment and prevention of osteoporosis. Studies have shown that the anti-tumor and anti-angiogenic effects induced by suppressing VEGF expression are associated with BP, which suggests new areas of research for these drugs in tumorigenesis and angiogenesis. However, in ophthalmology, BP are known only as drugs that may cause uveitis, scleritis or orbital inflammation as rare side effects. BP were thought to accumulate mostly in bone tissue, but we suspected that they might have good permeability into the eye, possibly even causing side effects in rare cases. We have shown that BP have inhibitory effects on laser-induced CNV in mice, with suppression of VEGF expression. Recently, we also carried out a preliminary study of the therapeutic effects of BP in human CNV associated with age-related macular degeneration and pathological myopia.
In this study, we have assessed the visual outcomes of oral BP treatment in mCNV, and compared them with those of anti-VEGF therapy, photodynamic therapy with verteporfin (PDT) and natural course over 2 years of follow-up.
Abstract and Introduction
Abstract
Background Choroidal neovascularisation is often associated with pathological myopia. Bisphosphonates (BP), the preferred drug for treatment of osteoporosis, are known to have anti-angiogenic effects.
Objective To compare the therapeutic effects of oral BP with anti-vascular endothelial growth factor therapy (anti-VEGF) and photodynamic therapy (PDT) for myopic choroidal neovascularisation (mCNV) over 2 years of follow-up.
Methods One hundred eyes of 96 consecutive patients with mCNV who underwent oral BP treatment (alendronate 5 mg/day or 35 mg/week), anti-VEGF therapy, PDT or observation only were followed up for 2 years. The best-corrected visual acuity (BCVA) and the central retinal thickness (CRT) in optical coherence tomography were compared among the treatment groups.
Results The mean BCVA of the patients was maintained for up to 2 years in the BP and PDT groups. In the anti-VEGF group, the mean BCVA was significantly improved but was significantly worse in the no-treatment group. The visual outcomes were significantly better in the BP, PDT and anti-VEGF groups than the no-treatment group over 2 years of follow-up (−0.28, −0.26 and −0.39 logMAR units, p=0.032, 0.021 and 0.0004, respectively). The mean CRT was significantly decreased in all treatment groups (−84, −121 and −122 mm, p=0.0025, 0.017 and 0.000025, respectively).
Conclusions Oral BP should be investigated further as possible therapeutic and preventive drugs for mCNV.
Introduction
Pathological myopia is the leading cause of choroidal neovascularisation (CNV) in people under 50 years old. Patients with pathological myopia are common in Asian populations, including the Japanese population, and the number of patients has increased over the years. Myopic choroidal neovascularisation (mCNV) is a major complication of pathological myopia, which has a poor prognosis in its natural course; the visual acuity decreases to less than 20/200 in 89% of the eyes after 5 years.
Recently, a number of studies have reported that intravitreal injections of recombinant humanised monoclonal antibodies against vascular endothelial growth factor (VEGF), such as bevacisumab or ranibizumab, are effective against mCNV. However, repeated injections of anti-VEGF agents are needed to keep the lesion stable and to maintain vision, with one report indicating that a mean of 2.5 injections of ranibizumab or 4.7 injections of bevacizumab were required over 18 months of follow-up. These re-treatments may pose a cumulative risk of ocular and systemic complications such as endophthalmitis and strokes, and are a burden for patients and healthcare systems. Hence, we were interested in finding alternative treatments using oral drugs or eye drops, which are usually less expensive, easier to use and may also be used for prevention.
Bisphosphonates (BP) are powerful inhibitors of osteoclasts, and are the preferred drug for treatment and prevention of osteoporosis. Studies have shown that the anti-tumor and anti-angiogenic effects induced by suppressing VEGF expression are associated with BP, which suggests new areas of research for these drugs in tumorigenesis and angiogenesis. However, in ophthalmology, BP are known only as drugs that may cause uveitis, scleritis or orbital inflammation as rare side effects. BP were thought to accumulate mostly in bone tissue, but we suspected that they might have good permeability into the eye, possibly even causing side effects in rare cases. We have shown that BP have inhibitory effects on laser-induced CNV in mice, with suppression of VEGF expression. Recently, we also carried out a preliminary study of the therapeutic effects of BP in human CNV associated with age-related macular degeneration and pathological myopia.
In this study, we have assessed the visual outcomes of oral BP treatment in mCNV, and compared them with those of anti-VEGF therapy, photodynamic therapy with verteporfin (PDT) and natural course over 2 years of follow-up.
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