Treatment of Submacular Hemorrhage

Submacular hemorrhage is a rare but devastating sequel of choroidal neovascularization, which is a frequent complication of age-related macular degeneration (AMD).

It is serious because it interferes with visual acuity. The diagnostic workup is also made more difficult by the obstacles to visualization of the lesion, and therapies such as photocoagulation cannot be applied to this most sensitive region of the retina.

The natural history of a submacular hemorrhage, especially if due to AMD or if it is thick, is one of rapid decline of central vision. This is due to the disruption of the metabolic connections between the photoreceptor and retinal pigment epithelium (RPE) cells, with consequent loss of normal nutritive support and diffusion of products between them. Other important factors include the direct toxic action of iron and other byproducts of red blood cell degeneration, and a shearing effect on the peripheral parts of the retina by the contraction of the scar tissue formed by organization of the clot.

The earliest procedure used to treat submacular hemorrhage was vitreoretinal surgery. An incision was made through the retina in order to remove the clot using an irrigator or aspiratory. This involved a high risk of iatrogenic retinal or RPE damage.

This was followed by the use of intraocular recombinant tissue plasminogen activator (r-tPA). This offered multiple benefits, such as:

  • lowering the strength of the barrier formed by blood to metabolite diffusion
  • dilution of the released toxins
  • breaking down the fibrin network between the photoreceptors

The next step was taken by adding the infusion of an expansile gas, perfluoropropane (C3F8) gas, into the vitreous, to the intraocular injection of tPA. This was combined with face-down posturing for periods ranging from 1-3 days. This technique, which was termed pneumatic displacement, was based upon the probability that adequate diffusion of tPA into the submacular space took place, leading to clot liquefaction. This entry was supposed to occur through microscopic retinal rents formed by the stretching of the retina by the contained hemorrhage. If this is deficient, as is now suspected, the removal of the clot is accompanied by severe and permanent photoreceptor damage.

To address this concern, tPA was injected subretinally into the clot itself, followed by the pneumatic displacement of the liquefied hemorrhage through injected air. This fluid-air exchange is facilitated by upright positioning postoperatively. Since this did not involve major handling of the retina, but ensured access of the tPA to the blood clot, it seemed to offer better success rates with fewer complications. It avoided the intraoperative waiting time of up one hour for the clot to lyse, that was commonly observed in other techniques. The use of air rather than expansile gas avoided the complications seen with the latter, such as an increased risk of cataract formation or elevated pressure.

In later variations, the injection of tPA and air into the clot is practiced to reduce the buoyancy of the hemorrhage within the subretinal space, allowing it to displace inferiorly away from the fovea. Partial fluid-air exchange is carried out, and then sulfur hexafluoride (SF6) gas is introduced intravitreally. This prevents the air in the subretinal space from moving outside the macular area.

Still later, adjuvant therapy with injected antibodies to the vascular endothelial growth factor (VEGF) was shown to increase the rate of successful outcomes following treatment. Dobesilate has also been used as an inhibitor of microglial cell aggregation and activation, followed by fibroblast growth factor (FGF) production. FGF plays multiple roles in the development of the chronic inflammatory pattern, which is responsible for the poor outcome of subretinal hemorrhage.

References

Further Reading

Last Updated: Feb 27, 2019

Dr. Liji Thomas

Written by

Dr. Liji Thomas

Dr. Liji Thomas is an OB-GYN, who graduated from the Government Medical College, University of Calicut, Kerala, in 2001. Liji practiced as a full-time consultant in obstetrics/gynecology in a private hospital for a few years following her graduation. She has counseled hundreds of patients facing issues from pregnancy-related problems and infertility, and has been in charge of over 2,000 deliveries, striving always to achieve a normal delivery rather than operative.

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