Choroidal Neovascular Membranes Treatment & Management

Updated: Mar 01, 2017
  • Author: Steve Charles, MD; Chief Editor: Andrew A Dahl, MD, FACS  more...
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Treatment

Medical Care

Zinc/antioxidant therapy

In the Age-Related Eye Disease Study (AREDS), zinc combined with other antioxidants has been shown to reduce the progression rate of AMD by approximately 25% in patients with intermediate drusen. [54]

Intravitreal injection

Ranibizumab (Lucentis) is an anti-VEGF monoclonal antibody fragment. Intravitreal ranibizumab is safe and effective in stabilizing and improving vision in patients with choroidal neovascularization (CNV) caused by pathological myopia with a low number of injections. [55] The US Food and Drug Administration (FDA)-approved dose of ranibizumab is 0.5 mg (0.05 mL) administered by intravitreal injection [56, 57] for exudative AMD.

In pivotal Phase III clinical trials involving treatment of neovascular age-related macular degeneration (AMD), ranibizumab was administered once a month for up to 2 years. [58, 59, 60] The benefits of treatment with ranibizumab were also maintained in most patients for up to 2 years with continuous use. Treatment should be continued and monitored. Individual results may vary. In the pivotal clinical trials, some patients reported an improvement in vision starting at day 7 after treatment with ranibizumab. However, just because a patient does not report an immediate improvement, it does not mean that ranibizumab is not working. Some patients experience improvements later or merely do not lose significant vision with ranibizumab.

Compared to continual monthly dosing, dosing every 3 months will lead to an approximate 5-letter (1-line) loss of visual acuity benefit, on average, over the following 9 months. Patients should be evaluated regularly according to the package label.

Monthly injections were used in the pivotal clinical trials, but many retinal specialists have switched to a treat-and-extend paradigm primarily using OCT evidence of subretinal fluid and/or retinal edema as an indication for retreatment. Because of the concern that recurrences occasionally result in poor outcomes, most retinal specialists now use a treat-and-extend strategy; injections are given after leakage is eliminated, and the follow-up interval is extended to 6 weeks. If the lesion is dry at 6 weeks, another injection is given, and the follow-up interval is extended to 8 weeks.

Ranibizumab sets a new standard in the treatment of neovascular AMD because it is the first therapy proven to improve vision instead of simply slowing the decline of central vision loss. In clinical trials, up to 40% of patients gained 15 or more letters of vision and nearly all patients (up to 96%) maintained vision.

Of patients treated with ranibizumab, 94% remained on therapy for 1 year versus 89% of patients in the control groups. Ranibizumab has been studied in more than 1000 patients with neovascular AMD in 2 double-masked, controlled 2-year studies.

Ranibizumab is indicated for the treatment of patients with neovascular (wet) AMD.

Ranibizumab is contraindicated in patients with ocular or periocular infections.

Intravitreal injections, including those with ranibizumab, have been associated with endophthalmitis and retinal detachment. [61] Proper aseptic injection technique should always be used when administering ranibizumab. Patients should be monitored during the week following the injection to permit early treatment, should an infection occur.

Increases in intraocular pressure (IOP) have been noted within 60 minutes of intravitreal injection. IOP and perfusion of the optic nerve head should be monitored and managed appropriately.

Although a low rate (< 4%) of arterial thromboembolic events (ATEs) was observed in one ranibizumab clinical trial, a theoretical risk of ATEs exists following intravitreal use of VEGF inhibitors.

Serious adverse events related to the injection procedure occurring in less than 0.1% of intravitreal injections included endophthalmitis, rhegmatogenous retinal detachment, and iatrogenic traumatic cataract. Other serious ocular events occurring in less than 2% of patients included intraocular inflammation and increased IOP.

In clinical trials, the most common ocular adverse effects included conjunctival hemorrhage, eye pain, and vitreous floaters. The most common nonocular adverse effects included hypertension, nasopharyngitis, headache, and upper respiratory tract infection; none of which have been shown to be related to the drug. Aflibercept (Eylea; VEGF-Trap) is a soluble decoy receptor that binds VEGF and other vascular growth factors. It was approved by the FDA for the treatment of neovascular age-related macular degeneration (AMD) and other CNVs. 

In clinical trials, all aflibercept groups, including one group dosed only every two months, were noninferior and clinically equivalent to monthly ranibizumab for the primary endpoint (the 2q4, 0.5q4, and 2q8 regimens were 95.1%, 95.9%, and 95.1%, respectively, for VIEW 1, and 95.6%, 96.3%, and 95.6%, respectively, for VIEW 2, whereas monthly ranibizumab was 94.4% in both studies). In a prespecified integrated analysis of the 2 studies, all aflibercept regimens were within 0.5 letters of the reference ranibizumab for mean change in best corrected visual acuity (BCVA); all aflibercept regimens also produced similar improvements in anatomic measures. Ocular and systemic adverse events were similar across treatment groups. This led to the labelling of aflibercept for every-2-month administration after loading doses. Some medical retina experts suggest that aflibercept is more effective in patients with pigment epithelial detachments (PED). Clinical trials have shown that aflibercept is often effective in patients in whom ranibizumab or bevacizumab (Avastin) therapy has failed.

Bevacizumab is a larger anti-VEGF monoclonal antibody fragment that was originally developed to treat various types of cancer. Although unapproved by the FDA for treatment of CNV, monotherapy with bevacizumab is very effective and is widely used off-label for CNV not due to wet AMD.

Approximately 50% of retinal specialists use off-label bevacizumab instead of the FDA-approved ranibizumab or aflibercept, using a similar treatment schedule and indications for retreatment. The NEI-sponsored CATT trial was a head-to-head randomized multicenter comparison of ranibizumab to bevacizumab using with both monthly and PRN treatment arms. It revealed essentially no differences in efficacy, with a slightly higher number of adverse effects with bevacizumab.

Technique

Bevacizumab, ranibizumab, and aflibercept are administered through a fine 30- to 31-gauge needle, which most patients tolerate well.

A sterile intravitreal technique using povidone iodine; masks on the patient, tech and injecting physician; and a sterile bladed speculum are essential to reduce the risk of endophthalmitis.

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Surgical Care

In 1991, Thomas and Kaplan reported a series of patients operated on for subfoveal CNVMs secondary to POHS. [62] Subsequent series included CNVM associated with AMD, angioid streaks, myopic degeneration, and idiopathic CNVM. [63, 64, 65] Idiopathic cases have the best results, followed by POHS cases. Most studies showed poor results for patients with AMD (approximately 20% had better vision, 60% had the same vision, and 20% had worse vision). Some surgeons state that submacular surgery for CNVM in patients with AMD may result in stabilization. Again, it must be emphasized that this procedure may also result in complete loss of vision, which is not true of the natural course of the disease. Results of the Submacular Surgery Trial (SST) demonstrated that submacular surgery is ineffective in AMD and POHS.

RPE transplantation has been used for patients with AMD by some investigators; 100% of patients undergo rejection of cadaver RPE, requiring immune suppression in those patients without a life-threatening disease. [66] Transplanted RPE cells do not become adherent to the Bruch membrane so the RPE cells would have to be transplanted as a sheet in combination with the Bruch membrane and probably choriocapillaris. Use of nasal RPE and iris pigment epithelium is not effective; neither support the macular visual cycle. Many biologic, practical, and ethical issues are associated with sourcing RPE cells for transplantation. RPE transplantation is not a viable therapy. [67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86]

Macular translocation has been advocated for subfoveal CNVM. One procedure uses vitrectomy, creation of a total retinal detachment, and a 360-degree retinotomy followed by retinal rotation. An alternate method, termed limited macular translocation, is based on retinal detachment creation and scleral imbrication or outpouching. [87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 41, 42, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 79, 80, 149, 150, 151, 36, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161]

Many eyes have been lost as a result of retinal translocation. Bleeding, retinal detachment, proliferative vitreoretinopathy (PVR), macular holes, new neovascular membranes, and good anatomical results without visual improvement are frequent complications of translocation. [162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173] Significant aniseikonia, high astigmatism, diplopia, enophthalmos, and ptosis are associated with limited macular translocation. [174, 175, 176, 177] Major cycloversion and diplopia are associated with retinal rotation methods. [178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188] Neither form of translocation has sufficient safety and efficacy to be indicated.

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Consultations

In most cases, general ophthalmologists should consult retina specialists.

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Diet

Eating spinach, kale, mustard greens, turnip greens, collard greens, nuts, and oily fish reduce the progression rate of patients with signs of early AMD. Berries and other plant-based diet elements rich in antioxidants are also probably effective. Patients may respond to suggesting a diet consisting of relative high quantities of richly colored vegetables and fruits, the so-called rainbow diet.

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Activity

High blood pressure could theoretically result in bleeding from active neovascularization. Smoking increases the risk of AMD progression by 350-500%.

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