Introduction

The growth of choroidal neovascular membranes (CNV) beneath the macula usually causes significant disturbance of central visual function. Prior to the advent of photodynamic therapy and anti-vascular endothelial growth factor (anti-VEGF) agents, the only therapy of proven benefit compared with observation was thermal photocoagulation of the CNV.¹ During that era, surgical removal of subfoveal CNV of various etiologies was an alternative method of eradicating the CNV and improved visual function was achieved in a variety of etiologic settings. Even with current anti-VEGF agents, on occasion extensive subretinal hemorrhage occurs and surgical intervention is appropriate. Infrequently, surgical removal of CNV without hemorrhage is indicated. This chapter presents current concepts regarding the use of vitreoretinal surgical techniques as treatment of CNV with or without extensive hemorrhage.

Surgical technique

De Juan and Machemer first reported vitrectomy for the removal of macular CNV through large temporal retinal incisions.² Thomas and Kaplan subsequently modified the technique to utilize an eccentric, small retinotomy. Fluid was injected through the retinotomy, and manipulation and extraction of the CNV were achieved.^3,4 Face down positioning overnight proved adequate to close the small retinotomies without laser photocoagulation.⁵ Complications with this technique were minimal.

Early results

These surgical techniques were applied to macular CNV and favorable visual outcomes were reported for CNV of a variety of etiologies.^6–17 It was soon recognized that although some eyes regained excellent central visual function following removal of subfoveal CNV, others did not. Gass hypothesized that some CNV proliferate within Bruch’s membrane and beneath the retinal pigment epithelium (RPE), as well as beneath the neurosensory retina (Type I CNV – typical of AMD). Removal of such CNV would be expected to leave defects in RPE and result in poor vision. In other eyes, he postulated that CNV grow through relatively discrete defects in Bruch’s membrane and proliferate anterior to native RPE in the subneurosensory retinal space (Type II CNV – typical of histoplasmosis).¹⁸ Eyes with CNV associated with the ocular histoplasmosis syndrome, other chorioretinal inflammatory conditions, and idiopathic CNV indeed often demonstrated preserved central RPE and good foveal function after vitrectomy. Eccentricity of the choroidal ingrowth site was found to be an important prognostic factor for good vision in these cases with focal ingrowth sites.¹⁹ Recurrent CNV proved to be a major obstacle to good vision following surgery, as is the case with essentially all other therapies for choroidal neovascularization.²⁰

Submacular surgery trials

The Submacular Surgery Trials (SST) were four NIH-sponsored, multicenter, randomized, prospective trials conducted to compare outcomes of submacular surgery versus then-current standard therapy.²¹ The SST Pilot Trial of laser photocoagulation versus surgery for recurrent choroidal neovascularization secondary to age-related macular degeneration enrolled 70 patients with 34 receiving surgery and 36 laser. At 2-year follow-up, 65% of surgery eyes versus 50% of lasered eyes had vision more than one line worse than at baseline. The data offered no reason to prefer surgery over photocoagulation.²²

The SST Group N enrolled 454 patients with new subfoveal choroidal neovascularization secondary to AMD and randomly assigned patients to surgery or observation. Both groups declined in visual acuity from 20/100 at baseline to 20/400 by month 24, and the investigators concluded that surgery should not be recommended for these patients.²³

The SST Group H enrolled 225 patients, 18 years or older with new or recurrent subfoveal choroidal neovascularization that was either idiopathic or associated with ocular histoplasmosis.

At all time points, median visual acuity was better in the surgery group than in the observation group, but the difference did not reach statistical significance. At 24 months, median visual acuity was 20/250 for observation eyes and 20/160 for surgery eyes. Only those eyes with acuity worse than 20/100 at baseline achieved a significantly better outcome with surgery than observation at 24 months (76% versus 50%, respectively, for vision better or at most one line worse than initially measured). Of surgery eyes, 4% suffered retinal detachment and 58% of surgery eyes experienced recurrent neovascularization by month 24. The study concluded that submacular surgery may be considered in similar eyes with poor vision (worse than 20/100).²⁴

Current indications for surgical removal of CNV

In the era of anti-VEGF therapy, surgical removal of CNV is rarely appropriate. Possible indications would include large peripapillary CNV unresponsive to anti-VEGF agents and/or photodynamic therapy and too large for thermal laser photocoagulation.²⁵ In such extrafoveal lesions, the CNV can be removed to produce a small, quiet, atrophic scar around the nerve. If the fovea is involved in the neovascular process, then surgical extraction will likely lead to loss of foveal RPE in AMD and likely limited vision. However, in histoplasmosis, central RPE and reasonable visual acuity may be preserved.^26–31

Introduction

Subretinal hemorrhage, defined as blood located in the potential space between the RPE and the neurosensory retina, is a common manifestation of several diseases of the retina and choroid. The natural history of untreated, thick submacular hemorrhage is generally poor, probably due to a combination of the toxicity of subretinal blood, as well as the underlying pathology causing the hemorrhage. Over the past two decades, a variety of treatment options have become available. However, the results of these interventions are often disappointing, and the management of submacular hemorrhage remains a therapeutic challenge.

Etiology

Subretinal hemorrhage involving the macula is most often caused by CNV. Any macular condition that causes growth of CNV can therefore lead to submacular hemorrhage. In a series of 47 consecutive cases of submacular hemorrhage reported by Ibanez et al., over 80% were due to AMD with retinal arterial macroaneurysm and CNV due to histoplasmosis, angioid streaks, and idiopathic submacular hemorrhage being less common.³² Pathologic myopia and idiopathic polypoidal choroidal vasculopathy have also been reported as causes of submacular hemorrhage.^33,34 Trauma is another possible cause of submacular hemorrhage. This may occur either at the time of trauma due to localized choroidal rupture, or remotely due to the development of CNV at the edge of the rupture site.³⁵ Other sources of subretinal hemorrhage in the macula are rare.

Natural history

The natural history of untreated submacular hemorrhage has been described by several authors. Bennet et al.³⁵ described 29 eyes with submacular hemorrhage and found that the etiology was the most important factor in predicting the final visual outcome. In this series, of the 12 patients with AMD as the cause of the hemorrhage, 67% of the patients had unimproved or worsened visual acuity at the end of the follow-up period. The final mean visual acuity was 20/1700. Another study by Scupola et al.³⁶ examined 60 eyes with subretinal hemorrhage due to AMD, and confirmed this poor prognosis, with 80% of the eyes having a worse mean visual acuity of 20/1250. In contrast to this, in Bennet’s series, the five patients with traumatic choroidal rupture with subretinal hemorrhage fared much better. All five eyes improved, with mean visual acuity of 20/35.³⁵ Likewise, in a case series of 11 patients with subretinal hemorrhage due to Best disease, 10 of the 11 patients had improved, with a final mean visual acuity of 20/50.³⁷

The largest natural history study of AMD-associated subretinal hemorrhage to date is the observation arm of the Submacular Surgery Trials Group B in which 168 eyes with subfoveal choroidal neovascular lesions composed of at least 50% blood involving the foveal center and with initial visual acuity between 20/100 and light perception were followed for 2–3 years. Only 19% of eyes gained two or more lines of vision during follow-up, while loss of two or more lines occurred in 59% and 36% experienced severe vision loss of 6 lines or more. At 2 years, only 10% of eyes had visual acuity of 20/200 or better.³⁸

Management options

Given the generally poor natural history of submacular hemorrhage, especially when caused by AMD, many investigators have explored various treatments. Since patients with significant submacular hemorrhage have been excluded from all major, randomized, prospective clinical trials (except the SST) the ideal management for these patients remains uncertain. We present here some of the more commonly considered treatments for subretinal hemorrhage.