Optic atrophy secondary to sickle cell hyphema is avoidable

September 1, 2008

Optic atrophy secondary to sickle cell hyphema can lead to permanent loss of visual acuity. Sickling should be suspected in all cases of hyphema, particularly in individuals of African American or Mediterranean descent. Because a slit-lamp examination will not reveal sickled cells, however, a lab test for sickling should be ordered.

Baltimore-The "nasty surprise" of optic atrophy secondary to sickle cell hyphema is preventable, according to Morton F. Goldberg, MD, FACS.

"That's the most important message I can deliver," said Dr. Goldberg, who is the Joseph E. Green Professor of Ophthalmology and former director, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore.

In most cases, optic atrophy typically is neither seen nor suspected during traumatic hyphema in the presence of sickling erythrocytes because the optic nerve is not visible through the blood-clotted anterior chamber, Dr. Goldberg said. He added that this also is the case in postoperative hyphema as well as in trauma cases.

Dr. Goldberg also explained that a slit-lamp examination of an eye with hyphema will not reveal whether any cells are sickled, but this status can be determined by blood tests available at most laboratories. Results usually are available the same day.

Once the blood clot clears and the clinician can see through the anterior chamber to the optic nerve, Dr. Goldberg said, a "nasty surprise" may await: optic atrophy with its associated loss of visual acuity on a permanent basis. This vision loss may occur even if IOP never exceeds 30 mm Hg.

"There's something very special and unusual and deleterious about a hyphema associated with sickled red blood cells-loss of vision following only minimally to moderately elevated IOP," Dr. Goldberg said.

Sickle cell diseases are common; all genetic types sickle within the anterior chamber, and all types are dangerous in this clinical setting. It is important, therefore, to detect those individuals who have hyphema and might be carrying the sickle cell gene, Dr. Goldberg added.

Assertions about hyphema

He described a series of assertions about hyphema and optic atrophy, followed by clinical evidence and laboratory data validating them:

  • In the context of sickling, aqueous humor is the most noxious fluid in the body. Although this may seem counterintuitive to an ophthalmologist, it is aqueous that especially induces and maintains the sickling phenomena.

  • Sickle trait, the ordinarily benign form of the sickling syndromes, is just as dangerous as the systemically severe hemoglobinopathies when the blood is in the anterior chamber.

  • A sickle gene is common in individuals having African or Mediterranean ancestry, and up to 10% of African Americans in the United States carry at least one such gene.

  • Sickled cells are dangerous in the anterior chamber because they obstruct outflow of aqueous and lead to ocular hypertension. Also, in the patient with sickling, even mild IOP elevation can lead to irreversible optic atrophy and permanent loss of vision. Because vascular perfusion in such eyes can already be poor, it is easily made worse.

  • The clinician always should suspect sickling in the presence of ocular hyphema, particularly in African Americans and individuals of Mediterranean ancestry.

  • The clinical corollary is that paracentesis should be performed very early if sickling can be confirmed by the blood test and if hypotensive drugs (systemic medications as well as glaucomatous eye drops) and inspired oxygen are ineffective.

Dr. Goldberg then mentioned the "24-for-24 rule," which states that if the average IOP is greater than 24 mm Hg for any consecutive 24-hour period, the clinician should intervene immediately with routine paracentesis because it usually is curative.

Research

In his research on hyphema and optic atrophy, Dr. Goldberg has studied how red blood cells escape from the anterior chamber. He found that several escape channels exist, but the most important method is through the conventional outflow channels, through the trabecular meshwork, and into Schlemm?s canal. Because sickled cells are rigid and elongated, however, most are effectively filtered by the trabecular meshwork, and few get pushed into the canal by the pressure differential between it and the anterior chamber. The sickled red cells clog the meshwork and create a "logjam" that hinders the outflow of aqueous fluid.

Data from in vitro and in vivo studies also show that red blood cells preferentially sickle in the aqueous humor. Patients with sickle cell hemoglobinopathies have a greater percentage of sickled erythrocytes in their anterior chambers than in their circulating venous blood, he said.

He also tested the hypothesis that sickled cells cause disproportionately prolonged or severe ocular hypertension relative to what transpires in the presence of nonsickling cells. He injected all sickle cell types into living rabbit anterior chambers and compared the results with observations after injection of normal, nonsickled blood. The average duration of the hyphema after injection of sickle cells was longer than that after injection of nonsickled cells, and the elevation of IOP, defined as the average number of days with IOP greater than 50 mm Hg, was substantially higher when the cells were sickling than when they were not sickling.

"Note that this prolonged, highly elevated IOP resulted in spontaneous rupture of the globe in three rabbit eyes out of 23 injected, whereas none ruptured when they had been injected with nonsickling blood. This, obviously, was not a subtle phenomenon," Dr. Goldberg said.

He also studied whether sickle cell trait was any less serious in the hyphema model. He compared its effect on hyphema in rabbits against the results from more serious systemic hemoglobinopathies and found no change in the clinical phenomena.

"I was able to conclude from these in vivo studies of red cells in living rabbit eyes that the hyphema effects are more severe and more prolonged when the cells are capable of sickling. And in the case of sickle cell trait, it is no less dangerous than the systemically severe hemoglobin diseases insofar as the eyes are concerned," Dr. Goldberg said.

He also noted that the normal anterior chamber chemical and physical environment is quite different from what transpires in the viscera and the circulating blood of a living patient. The oxygen content in the anterior chamber is decidedly less and a unique, high concentration of ascorbic acid-a reducing agent-is present. Both of these phenomena induce and maintain sickling.

By looking at the effects of red and white blood cells in the rabbit anterior chamber on pH levels, pO2 (partial pressure of oxygen), and pCO2 (partial pressure of carbon dioxide), Dr. Goldberg also found that the pH level became much more acidic within about 3 hours of the introduction of blood into the chamber. The pO2 level, typically about 55 to 60 mm Hg in the normal rabbit aqueous, fell to about 38 mm Hg after 3 hours of incubation with the red and white cells. The pCO2 level rose commensurately.

Ascorbic acid concentration

His next step was to determine the effect on the sickling phenomena, if any, of the normally high concentration of ascorbic acid versus a low concentration. Dr. Goldberg tested the concept in guinea pigs because their ascorbic acid levels can be lowered by restricting the amount of vitamin C in their diet.

For the experiment, he injected blood with 19% of its cells sickled into the anterior chambers of guinea pigs with normally high levels of ascorbic acid. He found that the percentage of sickled cells tripled after several hours of incubation, whereas in animals with a vitamin C (ascorbate) deficiency, the percentage of cells becoming sickled only doubled. Similar results were obtained in experiments with rats having different ascorbic acid levels.

"The presence of a normally high level of vitamin C does maximize the sickling phenomenon," Dr. Goldberg said.

Treatment approaches

Therapeutic steps include hyperoxygenating the patient through a conventional face mask as well as a transcorneal delivery system, in addition to using pharmacologic agents to lower the IOP as quickly and as maximally as possible.

Medical therapy is conventional for glaucoma, except that osmotics should be used only once a day so as not to induce hemoconcentration, Dr. Goldberg said. He added that carbonic anhydrase inhibitors are very valuable, but methazolamide (Neptazane, Wyeth-Ayerst) is preferable to acetazolamide, because it is less likely to acidify the aqueous humor.

The therapeutic goal is to avoid optic nerve and macular ischemia, infarction, and atrophy as well as central or branch retinal artery occlusion. "Remember the 24-for-24 rule, and do an immediate paracentesis [if needed]. Although there are no controlled studies validating this therapeutic recommendation, it is derived from numerous reports in the literature and from my own personal observations as well," Dr. Goldberg said. "This is a routine procedure. The only caveat is to do it slowly so as not to decompress the eye rapidly and get a secondary rebleed.

"It is valuable to remember that even in the presence of central retinal artery occlusion or branch retinal artery occlusion, one can reverse the visual deficit, even if some swelling of the retina has occurred, if the paracentesis is performed quickly enough," he concluded.

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