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Purpose: To report a dramatic occlusive event of the macula surrounding the foveal avascular zone, causing severe and permanent loss of vision in a child with sickle cell disease., Methods: Case report. A nine-year-old boy with SS hemoglobinopathy and oculocutaneous albinism developed acute unilateral loss of vision., Results: Ophthalmoscopy revealed a pale, milky white, thickened retinal lesion centered on the fovea in the right eye as well as foveal hypoplasia in the left eye. The presence of macular malformation associated with oculocutaneous albinism precluded formation of a cherry-red spot. Fluorescein angiography of the right eye demonstrated extensive occlusions of the arterioles surrounding the foveal avascular zone. The presence of occlusions surrounding the fovea from multiple directions suggested the possibility of central retinal artery occlusion with migration of microemboli downstream., Conclusion: The patient, the youngest case reported, developed an irreversible macular infarction that was not improved by an exchange erythrocyte transfusion. He was placed on a long-term monthly transfusion protocol to protect his unaffected eye.

Purpose: To examine the histopathologic and morphometric features of neovascular lesions in human proliferative sickle cell retinopathy., Methods: Postmortem ocular tissue was obtained from three subjects (aged 20, 28, and 40 years) with SS hemoglobinopathy and prepared for adenosine diphosphatase flat-embedding. Morphometric analysis was performed before serial sectioning., Results: Numerous active and autoinfarcted lesions were found that represented virtually all stages in the life cycle of preretinal neovascularization. These formations ranged from single small loops extending from arteries and veins along the retinal surface to the typical complex, elevated sea fan formations. Sea fans developed at hairpin loops and at arteriovenous crossings. There was an average of 5.6 connections between sea fans and retinal vessels; of these, 45% were arteriolar, 52.5% were venular, and 2.6% were at the capillary level. Six of eight sea fans were located at arteriovenous crossings. Autoinfarction appeared to occur initially within the sea fan capillaries. The average height of sea fans was 123 microns above the retinal surface., Conclusions: Preretinal neovascularization in sickle cell retinopathy can arise from both the arterial and venous sides of the retinal vasculature and can assume a variety of morphologic configurations. Multiple feeding arterioles and draining venules are common, and autoinfarction appears to occur initially at the preretinal capillary level rather than at feeding arterioles. Arteriovenous crossings may be a preferential site for sea fan development.

Objective: To examine the sickle cell retina in dual perspective (vascular patterns en bloc and structure in serial sections) to gain new insights into sickle cell retinopathy., Methods: We analyzed the retinas of two patients with sickle cell disease (a 54-year-old patient with hemoglobin SC, heterozygous for the S and C mutation in the beta chain of the globin gene, and a 20-month-old patient with sickle cell anemia [SS], homozygous for the S mutation) using the previously described adenosine diphosphatase flat-embedding technique., Results: The dual-perspective analysis afforded by our technique revealed that the primary site of occlusions was located at the precapillary level. An unusual neovascular formation, the hairpin loop, was observed in both patients' retinas and appeared to result from recanalization of the wall of an occluded vessel. Many autoinfarcted pre-retinal neovascular formations were observed in the older SC patient. Two patent preretinal formations were studied in detail and their evolution appeared to be influenced by mechanical factors. The vessels appeared to have been extruded from the retina, perhaps owing to hydrostatic pressure secondary to downstream occlusions. Small pigmented lesions consisting of retinal pigment epithelial cells ensheathing channels that resembled autoinfarcted vessels were found in the eye of the SC patient., Conclusions: This study illustrates unusual morphological features of intraretinal and preretinal neovascularization and of chorioretinal lesions in sickle cell retinopathy and suggests alternative mechanisms for their formation.

Hydroxyurea has been shown to increase fetal hemoglobin (Hb F) production in patients with sickle cell disease and therefore has the potential to alleviate both the hemolytic and vaso-occlusive manifestations of the disease. Preliminary evidence indicates that recombinant human erythropoietin (rhEpo) may also induce Hb F. Three sickle cell anemia patients were treated with escalating doses of intravenous rhEpo and, subsequently, with daily oral hydroxyurea. After the optimal hydroxyurea dose was attained, rhEpo was added again. Two additional patients were treated with hydroxyurea alone. Treatment with rhEp, either alone or in combination with hydroxyurea, had no significant effect on the percentage of F reticulocytes or F cells. In contrast, hydroxyurea treatment was associated with a 1.5-fold to sevenfold increase in F cells and a 2.3- to 27-fold increase in the percentage of Hb F. In the three patients whose response reached a plateau, hydroxyurea treatment was associated with lessened hemolysis, decreased serum bilirubin and lactate dehydrogenase levels, and prolonged 51chromium-labeled RBC survival. Hydroxyurea treatment also resulted in decreased numbers of irreversibly sickled cells and in decreased sickling at partial oxygen saturation, increased oxygen affinity, increased total RBC cation content, and diminished potassium:chloride co-transport. All five patients treated with hydroxyurea experienced a decrease in severity and frequency of painful sickle crises. This study confirms that hydroxyurea therapy increases Hb F production and provides objective evidence of a significant reduction in hemolytic rate and intracellular polymerization. In contrast, rhEpo, either alone or in combination with hydroxyurea, offered no measurable benefit. Based on these encouraging preliminary data, large-scale, controlled clinical trials are warranted to study the safety and efficacy of hydroxyurea in the treatment of sickle cell disease.

Long-term follow-up of patients enrolled in a randomized prospective trial of feeder vessel photocoagulation for proliferative sickle retinopathy has been completed. Of the 44 patients enrolled in Chicago, nearly a decade follow-up has been achieved on 29 patients (45 eyes). There were 20 control untreated eyes and 25 argon laser-treated eyes. Prolonged loss of visual acuity was rare in both groups. Argon laser photocoagulation has had a sustained effect on reducing the incidence of vitreous hemorrhage and visual loss from vitreous hemorrhage. Nine (45%) of 20 control eyes had vitreous hemorrhage, and it was recurrent in six (66%) of these nine eyes. A single episode was the only hemorrhagic event in the treated eyes. The laser-induced complications of choroidal neovascularization or retinal detachment were not associated with long-term visual sequelae. New sea fan evolution in 47% of study eyes suggests that these patients require long-term surveillance.

Background: Hydroxyurea increases the production of fetal hemoglobin (hemoglobin F) in patients with sickle cell anemia and therefore has the potential for alleviating both the hemolytic and vaso-occlusive manifestations of the disease. There is preliminary evidence that recombinant human erythropoietin may also increase hemoglobin F production., Methods and Results: We treated five patients with sickle cell disease with escalating doses of intravenous erythropoietin for eight weeks. Three of these patients were subsequently treated with daily doses of oral hydroxyurea. After the optimal dose was determined, erythropoietin was then given along with hydroxyurea for four weeks. Treatment with erythropoietin, either alone or in combination with hydroxyurea, had no significant effect on the percentage of hemoglobin F-containing reticulocytes (F reticulocytes) or red cells (F cells). In contrast, hydroxyurea treatment was associated with a 3-to-25-fold increase in F reticulocytes, a 1.6-to-7-fold increase in F cells, and a 2.3-to-16-fold increase in the percentage of hemoglobin F. In all three patients given hydroxyurea, treatment with this drug was associated with reduced hemolysis, shown by decreases in serum bilirubin and lactic dehydrogenase and prolongation of red-cell survival. Hydroxyurea treatment also resulted in a decrease in the percentage of irreversibly sickled cells and sickling at partial oxygen saturation, an increase in oxygen affinity and total red-cell cation content, and a reduction in potassium-chloride cotransport. All three patients had a decrease in the number of pain crises., Conclusions: This study confirms that hydroxyurea therapy increases hemoglobin F production and provides objective evidence that hydroxyurea reduces the rate of hemolysis and intracellular polymerization of hemoglobin S. In contrast, recombinant human erythropoietin, whether alone or in combination with hydroxyurea, offers no measurable benefit.

Injection of sickle cell erythrocytes (SS, SC, Sthal, and AS) into the anterior chambers of living human, monkey, and guinea pig eyes resulted in conversion of erythrocytes to the sickled configuration. Immune responses did not appear to play an important role in influencing this phenomenon. The number of cells sickled was directly related to the concentration of hemoglobin S. In human and monkey eyes, the severity of elevated IOP appeared to be related to the type of cells injected and their concentration of hemoglobin S. Even the ordinarily benign genotype of sickle cell trait demonstrated sickling in the anterior chamber and elevation of the IOP.

Sickle cell retinopathy in its advanced form is complicated by preretinal neovascularization, vitreous hemorrhage, and retinal detachment. Treatment of neovascularization can be performed with photocoagulation. Complications such as retinal breaks, retinal detachments, and choroidally fed neovascularization may result from such treatment. The risks vs. the benefits of various types of photocoagulation are currently being evaluated. Cryotherapy also may be used to treat neovascularization. It is currently being used in eyes with media that are too hazy to permit photocoagulation. It is used commonly during scleral buckling and vitrectomy procedures. In eyes with decreased visual acuity secondary to prolonged vitreous hemorrhage, pars plana vitrectomy can be utilized to produce optically clear media. Complications (including erythrocyte-induced glaucoma), however, may be severe. Retinal detachment can be treated by scleral buckling, but the markedly increased risk of anterior segment ischemia in patients with sickle cell hemoglobin necessitates preoperative, intraoperative, and postoperative prophylactic measures to minimize the risk of this potentially devastating complication. In eyes with retinal detachment with cloudy media and severe vitreous traction, combined scleral buckling and vitrectomy may be necessary. These eyes are extremely fragile, and a successful result is currently obtained in only about 50% of such cases. Hyphemas in patients with sickle cell hemoglobinopathies, whether traumatically or surgically induced, may have devastating effects on the eye. If elevated IOP results decreased vascular perfusion of the eye may cause irreversible damage to the retina and optic nerve. Most antiglaucoma medications, when used in the sickle cell patient, have a narrow margin of safety. Therefore, early surgical intervention for the treatment of sickle cell hyphemas is currently being evaluated.

In vivo incubations of Hgb SC erythrocytes showed significantly more sickling in anterior chambers characterized by high concentrations of ascorbic acid than in anterior chambers with low concentrations of ascorbic acid (normal guinea pigs compared with scorbutic guinea pigs and normal guinea pigs compared with normal rats). Low concentrations of ascorbic acid, however, did not completely eliminate intracameral sickling. Because acetazolamide raises the concentration of aqueous humor ascorbate, it should be used with considerable discretion when treating hyphema and secondary glaucoma caused by sickle cells. Methazolamide may be more desirable.

The Japanese sika deep (Cervus nippon) proved to be a suitable animal model for the study of acute phases of in vivo erythrocyte sickling. Ophthalmologic studies can be conducted during or after 1 to 6 hours of effective in vivo sickling. Intravenous administration of 1.75 to 3.5% sodium bicarbonate solution at a rate of 500 to 1,000 ml per hour produced a transient state of alkalosis and in vivo erythrocyte sickling in the sika deer. The percentage of sickled erythrocytes increased as the blood pH increased. Concurrently, the packed cell volume decreased. Sickling was enhanced by 100% oxygen ventilation after endotracheal intubation and light anesthetization. After the induction of erythrocyte sickling, a sickling-reversal phenomenon occurred despite continued bicarbonate administration. During the course of this reversal, the percentage of sickled erythrocytes steadily decreased, the venous blood pH decreased, and the packed cell volume slowly increased. Because of the sickling-reversal phenomenon, chronic erythrocyte sickling was not achieved.

A young black girl with sickle cell B+ thalassemia sustained macular infarction of the right eye due to multiple arteriolar occlusions. Follow-up examination revealed optic atrophy as well as microvascular abnormalities of the right macula. To the authors' knowledge, this is the first reported case of macular infarction in sickle cell B+ thalassemia.

With prospective observations we have documented by fluorescein angiography the development of retinal neovascularization in the eyes of patients with sickle cell-hemoglobin C disease (hemoglobin SC). In each patient, arteriolarvenular (AV) anastomoses occurred before the development of neovascular sea fans. To our knowledge, this report constitutes the first such documentation in the literature. New sea fans from AV anastomoses appeared throughout an average interval of 18 months (range, 8 to 36 months) in approximately 21% of young adults with hemoglobin SC. Each year approximately 14% of young patients with hemoglobin SC may develop retinal neovascularization.

Four patients with sickle cell hemoglobinopathies (one SC, three AS) and hyphemas were found to have more erythrocytes sickled in their anterior chambers than in their circulating venous blood. Intraocular pressure was severely elevated, despite relatively small amounts of intracameral blood. Systemic hypotensive agents were not always successful in reducing IOP, and in patients with sickle cell hemoglobinopathy, are probably contraindicated in high or repeated dose regimens. Moderate elevation of IOP in sickle cell hemoglobinopathy patients may produce rapid deterioration of visual function, perhaps because of a greater than usual effect on vascular perfusion in the central retinal artery and optic nerve. Early anterior chamber paracentesis may be the best treatment for this type of hyphema-induced secondary glaucoma.

Complete closure of retinal neovascularisation due to proliferative sickle cell retinopathy was achieved in 28 'sea fans' (areas of neovascularisation) in 9 eyes of 9 patients by means of a triple freeze-thaw technique. However, 2 eyes developed subsequent rhegmatogenous retinal detachments, presumably related to vitreous traction on necrotic retina. We therefore recommend photocoagulation as the best treatment of proliferative sickle cell retinopathy. If opacities in the media prevent photocoagulation, a single freeze-thaw cycle is preferable.

Neovascularization of the retina occurs in several types of sickle cell hemoglobinopathies and is highly characteristic in appearance. It arises in the equatorial plane of the fundus following preliminary arteriolar occlusions and arteriolar-venular anastomoses. Neovascular sea fans arise at the interface of perfused and nonperfused portions of the retina, starting during the first decade of life and continuing for many years thereafter. Although some sea fans undergo spontaneous autoinfarction, most show progressive growth and constant intravitreal transudation of plasma components. Traction on the sea fans and the retina results in bleeding into the vitreous, retinal tears, and retinal detachment. Therapeutic intervention with a variety of coagulative techniques is feasible and is usually indicated whenever sea fans are discovered. All therapeutic modalities are capable of inducing significant complications. This is particularly true of argon laser photocoagulation when energy is concentrated into small areas (less than 200 mu) for short durations (less than 0.2 second). With appropriate precautions, photocoagulation results in a high rate of successful obliteration of neovascular tissue. Both vitrectomy and scleral buckling are valuable therapeutic procedures, but both have disproportionately high complication rates in eyes with the propensity for intravascular sickling of erythrocytes. Specific prophylactic measures are therefore indicated when these operative techniques are employed in patients with sickle cell diseases.

In a prospective study of 38 patients, who were initially selected as being at an early stage of sickling retinopathy, three developed circular black chorio-retinal scars (black sunbursts) during a period of 6 to 24 months. These lesions appear to be the sequelae of intraretinal and subretinal haemorrhage. They occur in the fundus periphery and do not interfere with vision.

The number of erythrocytes adopting the sickled configuration in rabbit aqueous was determined with a masked counting technique in vitro and in vivo. The percentage of cells that became sickled in aqueous humor was greater than that observed in a control salt solution and in the donor blood itself. Aqueous humor, therefore, can be considered a particularly deleterious medium for erythrocytes having a propensity for sickling. Blood samples from six donors with systemically severe hemoglobinopathies (SC, Sthal, and SS) had relatively high levels of hemoglobin S and, in general, showed faster and more frequent sickling than did blood samples from donors with low levels of hemoglobin S (one SS patient, whose chronic blood transfusion regimen had replaced most of his hemoglobin S with normal hemoglobin, and two AS patients). Even erythrocytes from sickle cell trait cases, however, were capable of sickling when immersed in acqueous humor.

Six patients with proliferative sickle cell retinopathy and vitreous bands were treated with the neodymium-YAG (Nd-YAG) laser to accomplish lysis of avascular traction bands or to clear the media in front of the macula. Transection of bands was possible in five of the six cases but in two of these the effect was only partial. Three cases were satisfactorily treated with the Nd-YAG laser application alone, two eventually required conventional vitreoretinal surgery, and one patient's condition stabilized despite failure of the treatment. Complications from the treatment occurred in three cases and included subretinal (choroidal) hemorrhage, preretinal hemorrhage, microperforation of a retinal vein, and focal areas of damage to the retinal pigment epithelium. Neodymium-YAG vitreolysis may be a useful modality in carefully selected patients with proliferative sickle cell retinopathy, but potentially sight-threatening complications may occur.

The unique problems encountered in sickle patients include the need to remove peripheral vitreous if perfusing sea fans-which can bleed after vitrectomy-are present at the time of surgery. However, peripheral vitrectomy is riskier than central vitrectomy alone. If visualization of the sea fans is sufficient, it is safer to close the sea fans prior to vitrectomy in order to obviate the need for peripheral vitrectomy; then, only central vitrectomy is performed. When sea fans cannot be closed prior to vitrectomy, peripheral vitreous is removed to allow early photocoagulation of the sea fans before they bleed again. Four case presentations illustrate these principles. Vitrectomy relieved severe vitreous traction that complicated retinal detachment in the fifth patient, thereby eliminating the need for a tight encircling structure, which can be poorly tolerated in patients with SC hemoglobin.

Sickled erythrocytes leave the anterior chamber of human and monkey eyes by several mechanisms: intracameral and intratrabecular hemolysis and phagocytosis; entry into and phagocytosis within the iris and ciliary body; and passage into Schlemm's canal. Sickled erythrocytes used as biologic tracers allowed definite confirmation, for the first time in the human, that intracameral erythrocytes can enter Schlemm's canal in the orthograde direction. Erythrocytes appeared to traverse the inner wall of Schlemm's canal through the cytoplasm of individual endothelial cells, rather than between adjacent endothelial cells -- a mechanism similar to that employed by red and white blood cells elsewhere in the body. Although some sickled erythrocytes did pass into Schlemm's canal, considerable obstruction appeared to occur at the corneoscleral meshwork, juxtacanalicular connective tissue, and inner wall of Schlemm's canal, caused largely by the elongated, rigid nature of the sickled cells. Total blockage of Schlemm's canal was not observed.

Four patients with sickle cell hemoglobinopathies (one SC; three AS) and hyphemas were found to have more erythrocytes sickled in their anterior chambers than in their circulating venous blood. Intraocular pressure was severely elevated, despite relatively small amounts of intracameral blood. Systemic hypotensive agents were not always successful in reducing IOP, and in patients with sickle cell hemoglobinopathy, are probably contraindicated in high or repeated dose regimens. Moderate elevation of IOP in sickle cell hemoglobinopathy patients may produce rapid deterioration of visual function, perhaps because of a greater effect on vascular perfusion in the CRA and optic nerve. Early anterior chamber paracentesis may be the best treatment for this type of hyphema-induced secondary glaucoma.

Seven patients had sickle cell trait (hemoglobin AS) and vasoproliferative retinopathy. The retinal abnormalities in these seven patients were indistinguishable from those seen in patients with clinically significant sickling hemoglobinopathies (sickle cell-hemoglobin C disease, hemoglobin S-thalassemia disease, and sickle cell anemia). All seven patients also had some evidence of associated systemic disease such as diabetes, syphilis, tuberculosis, or sarcoidosis. In the presence of an associated systemic disease, marked retinopathy can occur in the ordinarily benign condition of sickle cell trait.

Transconjunctival cryocoagulation was used to treat proliferative sickle retinopathy in 6 patients. Ten eyes were treated with a single freeze-thaw cycle and were observed for 3 to 18 months. Nine of 13 (70%) neovascular lesions were completely closed without occluding major vascular trunks, while the remaining 4 (30%) showed marked attenuation.

James B. Herrick's 1910 article presenting the case of an anemic West Indian student with peculiar-shaped red blood cells was the first description of sickle cell anemia in Western medical literature. However, he told only part of the story. Records in Chicago, Washington, DC, and Grenada, West Indies, reveal more information about the events surrounding Herrick's discovery and help put them in historical perspective. Herrick's intern, Ernest E. Irons, abreast of the latest developments in medicine, actually performed the blood work and alerted Herrick about the odd-looking cells. Changing patterns in American race relations allowed the patient, Walter Clement Noel, to study dentistry in Chicago. He continued to receive care from Irons for 2 1/2 years, then returned to Grenada to practice dentistry. Noel died nine years after his return to Grenada, at age 32.

We analyzed 22 sickle cell trait hyphemas. Fourteen of the 22 eyes were adequately controlled with medical therapy alone, ie, the intraocular pressure averaged less than 25 mm Hg during consecutive 24-hour periods and there were no repeated transient rises of IOP above 30 mm Hg. Surgery was performed in eight eyes, because of inadequate medical control. Thirteen of the 14 medically treated eyes had acceptable levels of IOP within the first 24 hours; only one of the eight surgically treated eyes had adequate control during the first 24 hours. This suggests that control during the first 24 hours portends a good prognosis, while lack of control during that period predicts continued difficulty managing the IOP. This seems to be important in view of previous experience that suggests that these eyes do not tolerate minimal to moderate elevations in IOP as well as those of patients without sickle cell anemia.

Sixty-five patients with hemoglobins AS, SC, and SS were investigated in a masked fashion. We observed a statistically significant positive correlation between the severity of conjunctival sickling signs and the counts of irreversibly sickled cells in each hemoglobinopathy group. We also observed a statistically significant positive correlation between the severity of the conjunctival vasculopathy and the percentage of sickle hemoglobin in the total group of patients with hemoglobins AS, SC, and SS.

Eighteen patients (19 eyes) with sickling hemoglobinopathies underwent vitrectomy or scleral buckling operations. The indications for surgery were tractional or rhegmatogenous retinal detachment or vitreous hemorrhage. The retina was reattached in all four patients with rhegmatogenous detachments requiring scleral buckling surgery but no vitrectomy. All had excellent visual acuity postoperatively. Four of the five patients with vitreous hemorrhage requiring vitrectomy without buckling had substantial improvement in visual acuity. In ten patients with vitreous hemorrhage with either preexisting or iatrogenic retinal breaks, rhegmatogenous detachment, or tractional detachment, the rate of improvement in visual acuity was only 50%. Problems associated with vitreous or retinal surgery in patients with sickling hemoglobinopathies include iatrogenic retinal breaks, intraocular bleeding and secondary glaucoma, anterior segment ischemia, and systemic sickling.

Delayed development of choroidally fed neovascularization represents a potentially serious complication of feeder vessel photocoagulation of proliferative sickle cell retinopathy (PSR). Of the 53 photocoagulated eyes, choroidally fed neovascularization developed in 21 within one month to seven years (mean, 32.8 months). This complication appeared in eyes treated with argon laser and xenon arc. In 11, neovascular tissue remained flat in the chorioretinal scar (chorioretinal neovascularization), but in ten, the vessels grew into the vitreous (choriovitreal neovascularization). In many cases of chorioretinal neovascularization, the only subsequent complication was local vitreous hemorrhage. Visual acuities remained near normal. The development of choriovitreal neovascularization was associated with vitreous hemorrhages or retinal detachment in six of ten cases. Final visual acuities, however, were 20/50 or better in nine. Photocoagulation in some cases converted chorioretinal neovascularization to choriovitreal neovascularization or seemed to stimulate further growth of choriovitreal neovascularization. We now recommend no treatment for most cases of choroidally fed neovascularization. Photocoagulation techniques for PSR should attempt to minimize the development of choroidally fed neovascularization.

Fifteen patients (16 eyes) with proliferative sickle retinopathy treated with argon or xenon arc feeder vessel photocoagulation had chorioretinal (CRN) or choriovitreal (CVN) neovascularization develop. These patients were followed from 2 1/2 to 11 1/2 years with a mean follow-up of 6 years and 8 months. Clinically important late complications of the choroidal neovascularization included vitreous hemorrhage (in three of eight patients with CVN). However, in only two of these three eyes was there any drop in vision related to residual vitreous hemorrhage, and this was limited to loss of only one line of Snellen visual acuity. Therefore, treatment is not usually recommended if CRN or CVN develops after intense photocoagulation. Vitreous fluorophotometry was performed on these patients to examine the breakdown of the blood-retinal barrier. This gave a quantitative measure of fluorescein leakage not obtained with fluorescein angiography. Midvitreous measurements, which are more representative of these peripherally located proliferative lesions than are pre-retinal measurements, suggest that vitreous fluorophotometry may be helpful in differentiating the higher leakage of CVN from the CRN.

Macular ischaemia has a central role in the pathophysiology and prognosis of retinal macular disease. We attempted to quantitate two of its major components as follows: vascular nonperfusion, by measuring the foveal avascular zone (FAZ), using fluorescein angiography; and functional damage, using automated perimetry of the central 30 degrees. Sickle cell disease was chosen for study because it was considered a prototype for a purely ischaemic retinopathy without an exudative component. We found that the FAZ measurement was reproducible and that the patients with maculopathy had statistically larger FAZs than the normal controls (p = 0.016, Wilcoxon rank sum test). In addition, scotomas measured by visual field perimetry were significantly larger in the sickle cell patients with maculopathy than in those without maculopathy. Our results showed that angiography and perimetry of the central 30 degrees were more sensitive tests for the detection of ischaemic macular disease than visual acuity and that macular ischaemia could be quantified by their use.

We treated sea-fan neovascularization in 19 patients (21 eyes) who had proliferative sickle cell retinopathy with localized scatter photocoagulation. We placed burns of light to moderate intensity adjacent to 45 sea fans in a scatter fashion. In general, treatment extended from 1.5 mm posterior to 1.5 mm anterior to the sea fan and one clock hour to each side of each lesion. Flat sea fans responded dramatically to treatment, with complete regression in 24 of 28 lesions. Elevated sea fans (especially large ones) responded less rapidly, with complete regression in only four of 17 lesions. Localized scatter photocoagulation is valuable in treating patients with early proliferative sickle cell retinopathy.

The ultrastructure of rubeosis iridis in sickle cell-hemoglobin C disease is described for the first time. Findings included open interendothelial cell junctions, intraendothelial cytoplasmic attenuations (fenestrations), and pericyte formation. The ultrastructural appearance of rubeosis iridis gives no clue to the underlying etiology and is similar to that reported in rubeosis associated with diabetes mellitus, central retinal vein occlusion, and uveitis. The electron microscopic findings explain the functional incompetence of rubeotic vessels that are manifested by transmural leakage of fluorescein.

Retinal breaks developed in four eyes of four patients with hemoglobin SC disease and advanced proliferative sickle cell retinopathy (PSR) after argon laser photocoagulation of feeder vessels. These cases represented 8.7% of the 46 eyes with PSR treated with the argon laser at our institution in 1977 and 1978. In three patients, the retinal breaks were immediately adjacent to the site of photocoagulation. A scleral buckling procedure was necessary in only one of the four eyes; the breaks were successfully managed in the other three cases by encirclement with further laser treatment. None of the four eyes lost vision. In patients with vitreous traction in association with seafan neovascularization, argon laser photocoagulation may result in retinal breaks and retinal detachment.

The ocular manifestations of sickle cell hemoglobinopathies, while often not severe enough to affect vision, may develop in proliferative stages, resulting in arteriolar-venular anastomoses, neovascular proliferations, vitreous hemorrhage and retinal detachment. The authors review the historical, biochemical, and geographic aspects of the disease, and provide detailed descriptions of findings in theconjunctiva, uvea and fundus, with particular emphasis on the retina. Pathogenesis, histopathologic and clinical appearance, and modes of treatment are discussed.

Experimental sickle cell hyphemas were produced by injecting human sickle cell-beta(0)-thalassemia blood into rabbit anterior chambers. Eyes treated with topical 2% epinephrine hydrochloride showed no significant difference in the duration of the hyphema or in the percentage of sickled cells in the anterior chamber compared with untreated eyes. Topical 2% epinephrine had no apparent sustained effect on intraocular pressure.

Periodic photographic and angiographic surveys of patients with the earliest stages of sickle retinopathy showed a number of fundus findings. In seven cases (sickle cell anemia, four; sickle cell hemoglobin C, three), these findings included: (1) a variety of vascular abnormalities in the equatorial and post-equatorial retina such as segmented dilations of the vessel walls, hairpin-shaped vascular loops, hypertrophic, tortuous A-V anastomoses, intraluminal plugs, closure and loss of capillary bed, and terminal budding of capillaries; and (2) a continuous, spontaneous remodeling of the peripheral retinal vasculature due to successive closures and reopenings of equatorial retinal vessels. A centripetal recession of the peripheral retinal vasculature usually resulted. No correlation between the ophthalmoscopic and the systemic condition of the patients could be made.

When injected into rabbit anterior chambers, human sickle cell erythrocytes cause more intense and prolonged effects than do nonsickling erythrocytes. The consequences of injected sickle cell trait erythrocytes are not less severe than those of injected SC, SS, and Sthal erythrocytes. Regardless of hemoglobin composition, blood with a higher hematocrit value causes more severe complications than blood with a lower hematocrit value.

Nine female Japanese sika deer (Cervus nippon) were used in a total of 25 experiments in which sickling was chemically induced. During these experiments, color fundic and color fluorescein photographs were taken. Fundic changes included retinal vascular attenuation, blood column pallor, and decreased tapetal reflectivity. These changes were most likely directly associated with a decreased hematocrit and a generalized shocklike condition. Three deer had a congested appearance in retinal blood vessels and tapetum lucidum. Two of the 3 deer developed serous detachment of the retina. These changes seemingly were associated with severe venous statis; all 3 deer died shortly after the experiment was terminated. These experiments yielded data only for the acutely affected deer. None of the ocular changes could be considered the result of chronic sickling because of the reversal of sickling that occurred despite continued intravenous administration of bicarbonate. None of the deer developed ocular changes characteristic of sickle cell retinopathy in human beings. The changes in human beings probably result from continued stress and prolongation of sickling, and especially from a multiplicity of repeated severe episodes of sickling occurring over many years.

The disc sign is the presence of dark red spots on the optic disc of patients with a sickling hemoglobinopathy. The dark spots appear to be plugs of deoxygenated erythrocytes in small surface disc vessels. The occlusions, which are transient and do not produce clinically detectable visual impairment, were seen most often in patients with homozygous sickle cell anemia and may be the result of clogging of small vessels by irreversibly sickled erythrocytes.

Four patients with sickle cell hemoglobinopathies (one sickle cell hemoglobin C disease (SC); three sickle cell trait (AS)) and hyphemas had a higher percentage of erythrocytes sickled in their anterior chambers than in their circulating venous blood. Intraocular pressure (IOP) was severely increased, despite relatively small amounts of intracameral blood. Systemic hypotensive agents were not always successful in reducing IOP, and in patients with sickle cell hemoglobinopathy, are probably contraindicated in high or repeated dose regimens. Moderate increase of IOP in sickle cell hemoglobinopathy patients may produced rapid deterioration of visual function, because of a greater than usual effect on vascular perfusion in the central retinal artery and optic nerve. Early anterior chamber paracentesis may be the best treatment for this type of hyphema-induced secondary glaucoma.

Two distinct episodes of posterior ciliary artery occlusion were studied in a 32-year-old man with hemoglobin SS disease and multiple episodes of amaurosis fugax. Although posterior ciliary artery occlusions have been observed following photocoagulation of sickle cell retinopathy, their spontaneous evolution in patients with sickling hemoglobinopathies has received little attention. The manifestations of posterior ciliar artery occlusion seen in this case and in other clinical and experimental situations are reviewed. Histopathologic examination of three additional eyes of patients with sickle hemoglobinopathies revealed changes which may have been the result of previous small posterior ciliary artery occlusions or small vessel occlusive disease related to the sickling hemoglobinopathies; these cases are also reported.

Five patients had angioid streaks associated with sickle cell haemoglobinopathy. Other diseases associated with angioid streaks were ruled out, as was elastic tissue degenegation in sickle cell patients. After studying over 350 patients, we believe the incidence of angioid streaks in sickle cell disease to be between 1 and 2 per cent.