Proliferative Sickle Cell Retinopathy Research Articles

Clinical and Laboratory Factors Associated With the Severity of Proliferative Sickle Cell Retinopathy in Patients With Sickle Cell Hemoglobin C (SC) and Homozygous Sickle Cell (SS) Disease

Proliferative sickle cell retinopathy (PSCR) is the most frequent vision-threatening complication of sickle cell disease (SCD). We investigated the relationship between the severity of sickle cell retinopathy in heterozygous (SC) or homozygous (SS) adult SCD patients and the clinical and laboratory data obtained during visits to a national SCD referral center. This retrospective longitudinal analysis included 942 SCD patients (313 patients with SC and 629 with SS disease) with ophthalmologic evaluations who were followed over a 19-year period by a multidisciplinary team in a referral center. PSCR was graded using the Goldberg classification. We identified patient and SCD characteristics associated with sickle cell retinopathy severity using multinomial logistic-regression models. Multivariate analysis associated severe PSCR forms (stages III-V) with older age (p=0.032), pulmonary involvement (documented pulmonary hypertension with pulmonary arterial pressure≥40 mm Hg, restrictive syndrome>20%, or previous history of pulmonary embolism diagnosed by vascular imaging) (p=0.029), deafness or tinnitus (p=0.026), and no history of osteomyelitis (p=0.013) for SC patients; and with older age (p<0.001), male sex (p=0.003), and acute pyelonephritis (p=0.04) for SS patients. The model of severe PSCR versus no PSCR showed good calibration and discrimination for SC and SS patients. Awareness of the clinical and laboratory factors significantly associated with severe PSCR in patients with SC or SS SCD may contribute to improved preventive strategies.

Leukocoria and Vitreous Hemorrhage as the Initial Manifestation of Sickle Retinopathy in a 3-Year, 6-Month-Old Child With Sickle Trait (AS)

The authors present the youngest reported child with proliferative sickle retinopathy. A 3-year, 6-month-old boy presented with leukocoria in the left eye, left esotropia, and dense free-floating white vitreous cells obscuring the fundus, suspicious for endophytic retinoblastoma. Ultrasonography depicted dense debris in the vitreous with no distinct calcific echo or retinal mass. Transcorneal, transzonular fine-needle aspiration biopsy of the vitreous confirmed the presence of dehemoglobinized vitreous red blood cells without tumor. The opposite eye showed peripheral retinal pigment epithelial proliferation and fibrosis with angiographic peripheral ischemia. Hemoglobin electrophoresis disclosed sickle trait (AS). The findings were classified as proliferative sickle cell retinopathy with vitreous hemorrhage in the left eye and non-proliferative sickle cell retinopathy in the right eye. Leukocoria generally raises warnings for retinoblastoma, but can also reflect chronic vitreous hemorrhage.

DETECTION AND MONITORING OF SICKLE CELL RETINOPATHY USING ULTRA WIDE-FIELD COLOR PHOTOGRAPHY AND FLUORESCEIN ANGIOGRAPHY

In this study, we demonstrate the use of wide-field photography and fluorescein angiography to visualize the peripheral vascular changes and to identify patients with risk factors for developing proliferative sickle cell retinopathy. This is a retrospective case series of 12 eyes of 6 patients with sickle cell disease. Visual acuity testing, slit-lamp biomicroscopy, dilated fundus examinations, and noncontact wide-field fundus photography and fluorescein angiography using Optomap scanning laser ophthalmoscope (Optos, Marlborough, MA) were performed in all patients. The retinopathy was classified into proliferative and nonproliferative retinopathies, and the extent of retinopathy was measured in degrees. Wide-field images obtained using Optomap were compared with the derived seven-standard field images. At the time of initial examination, 50% of the total eyes had proliferative retinopathy. All the peripheral retinas and vasculature were easily imaged within a single frame with Optomap. Six eyes met the high-risk criteria for developing proliferative changes. None of the eyes in our case series had tractional retinal detachment. The degrees of any type of sickle cell retinopathy and active neovascularization ranged from 20° to 360° and 10° to 60°, respectively. In all but one eye, wide-field images detected peripheral vascular changes missed on the seven-standard field photographs. Wide-field fluorescein angiography and color photography enhance clinicians' ability to visualize peripheral vascular remodeling in sickle cell disease and to identify high-risk characteristics for proliferative sickle cell retinopathy.

Full-Thickness Macular Hole in a Patient With Proliferative Sickle Cell Retinopathy

Full-Thickness Macular Hole in a Patient With Proliferative Sickle Cell Retinopathy

Proliferative sickle cell retinopathy associated with sickle cell trait and gestational diabetes: case report

Proliferative sickle cell retinopathy is an uncommon complication in individuals with sickle cell trait (AS). However, the risk for proliferative retinopathy development is increased in patients with AS hemoglobinopathy associated with systemic conditions or ocular trauma. A case of a patient with AS hemoglobinopathy who developed proliferative sickle cell retinopathy after the occurrence of gestational diabetes and pregnancy-induced hypertension is reported. Hemoglobin electrophoresis revealed presence of A2 5.0%, S 35.0% and A 53.2%. The present case emphasizes the importance of evaluating systemic comorbidities in patients with sickle cell trait during pregnancy since sickle cell retinopathy can progress rapidly, as well as the importance of regular eye fundus examination in these patients.

Retinal Photocoagulation for Proliferative Sickle Cell Retinopathy: A Prospective Clinical Trial with New Sea Fan Classification

To compare the clinical outcome of stage III proliferative sickle cell retinopathy (PSR) treated by peripheral retinal scatter photocoagulation to natural course disease. Long-term follow-up of 101 patients enrolled in a prospective trial of photocoagulation for PSR has been completed. Among 202 eyes of 101 patients enrolled at the University Eye Clinic of Créteil, 73 eyes showed a stage III PSR, which the authors further divided into five new grades (A, B, C, D, E) considering size, hemorrhage, fibrosis, and visible vessels. Grading was based on a three-mirror fundus examination, 360 degrees color photographs, and fluorescein angiography. Mean follow- up was 4 years. Thirty-eight treated eyes and 35 untreated eyes were included in this study. The evolution was not statistically significant between treated and untreated groups concerning flat sea fan <1 MPS disc area (grade A) or elevated sea fan with partial fibrosis (grade C). Progression and regression were compared between the two groups for grade B, resulting statistically significant (p<0.05). Nine complications (13%) were observed, which only occurred in untreated patients with elevated sea fan and hemorrhage (grade B) or complete fibrosed sea fan with well defined vessels (grade E) (p<0.05). These data suggest that patients with grade A or C new sea fan classification should not be initially treated but observed.

Incidence and Natural History of Proliferative Sickle Cell Retinopathy: Observations from a Cohort Study

To describe the incidence, prevalence, and natural history of proliferative sickle cell retinopathy (PSR). Prospective longitudinal study over 20 years. Newborn screening of 100000 consecutive deliveries from 1973 to 1981 identified 315 children with homozygous sickle cell (SS) disease and 201 with SS-hemoglobin C (SC) disease. By the age of 5 years, 307 SS patients and 166 SC patients were alive and living in Jamaica and were recruited for this ophthalmic study. Description of retinal vascular changes on annual angiography and angioscopy. Incidence and prevalence of PSR and its behavior on follow-up. Progression of PSR was investigated using the number of eyes affected (none, one, both) and the interval until PSR onset. At last review in January 2000, PSR had developed in 59 patients (14 SS, 45 SC), unilaterally in 36 patients and bilaterally in 23. Incidence increased with age in both genotypes, with crude annual incidence rates of 0.5 cases (95% confidence interval [CI], 0.3-0.8) per 100 SS subjects and 2.5 cases (95% CI, 1.9-3.3) per 100 SC subjects. Prevalence was greater in SC disease, and by the ages of 24 to 26 years, PSR had occurred in 43% subjects with SC disease and in 14% subjects with SS disease. Patients with unilateral PSR had a 16% (11% SS, 17% SC) probability of regressing to no PSR and a 14% (16% SS, 13% SC) probability of progressing to bilateral PSR. Those with bilateral PSR had an 8% (8% SS, 8% SC) probability of regressing to unilateral PSR and a 1% (0 SS, 2% SC) probability of regressing to a PSR-free state. Irretrievable visual loss occurred in only 1 of 82 PSR-affected eyes, and 1 required detachment surgery and recovered normal visual acuity. Longitudinal observations over 20 years in a cohort of patients followed from birth confirms a greater incidence and severity of PSR in SC disease, and shows that spontaneous regression occurred in 32% of PSR-affected eyes. Permanent visual loss was uncommon in subjects observed up to the age of 26 years.

Visual Outcome after Laser Photocoagulation for Stage 4 Proliferative Sickle Cell Retinopathy

Objective: The objectives of this research is to evaluate the visual outcome after peripheral laser photo-coagulation for Goldberg stage-4 proliferative sickle cell retinopathy patients seen in Eye Foundation Hospital Lagos between January and December 2002. Methodology: A hospital-based retrospective case review study was done. The medical records of 10 patients (13 eyes) who were treated with laser photocoagulation for stage 4 proliferative sickle cell retinopathy within a 12 month period were evaluated. World Health Organization (WHO) visual acuity groupings were used for evaluation. Results: At presentation, 92.3% of the eyes had normal vision while 7.7% had visual impairment. At three months after laser treatment, 84.6% of the eyes had normal vision while 15.4% had visual impairment. At six months after treatment, 76.9% of the eyes had normal vision while 23.1% of eyes were blind due to recurrent uncontrollable vitreous haemorrhage. Out of the 13 eyes which were treated, 7.7% had actually improved from the visual impairment group to the normal vision group. Conclusion Peripheral laser photocoagulation is effective in the treatment of selected cases of stage 4 proliferative sickle cell retinopathy; with 76.9% of patients maintaining normal vision 6 months after treatment. Key Words: laser photocoagulation, sickle cell retinopathy, visual outcome Nigerian Journal of Ophthalmology Vol.12 (1) 2004: 19-22

Expression of pigment epithelium-derived factor (PEDF) and vascular endothelial growth factor (VEGF) in sickle cell retina and choroid

Pigment epithelium-derived factor (PEDF) has been shown to be an inhibitor of angiogenesis as well as a multipotent neurotrophic factor in the mammalian eye. Changes in PEDF levels have been correlated with development of retinal neovascularization in oxygen-induced retinopathy. The purpose of this study was to determine the localization and relative level of PEDF in human retinas and choroids using immunohistochemistry and evaluate the changes in PEDF and vascular endothelial growth factor (VEGF) localization and their relation to the progression of proliferative sickle cell retinopathy. Cryopreserved tissues from eyes of normal subjects and subjects with non-proliferative or proliferative sickle cell retinopathy were used with streptavidin peroxidase immunohistochemistry. A rabbit polyclonal antibody was made against recombinant human PEDF. Binding of the antibody was blocked by preincubation of the antibody with excess human recombinant PEDF. Relative levels of immunoreactivity were scored with a seven-point grading system and by microdensitometric analysis. The most prominent sites of PEDF localization in the normal eye were the vitreous condensed at the internal limiting membrane and RPE–Bruch's membrane–choriocapillaris complex. PEDF was also prominent in choroidal stroma. There was limited immunoreactivity in some cells of the neural retinas, in blood vessels and in the interphotoreceptor matrix (IPM). There was no difference in ratio (1·47 vs. 1·44) of PEDF/VEGF or the relative levels of either growth factor in the retinal vasculatures of the control subjects and perfused area of non-proliferative sickle cell retinas. The ratio was increased in the non-perfused area of the non-proliferative sickle cell retinas (2·24). In eyes with proliferative sickle cell retinopathy, elevated PEDF and VEGF immunostaining was present in viable vessels of sea fan neovascular formations as well as feeder vessels of sea fans. The PEDF/VEGF ratio in sea fans was 1·0. Immunoreactivity for PEDF was prominent in retinal vessels in non-perfused regions and in atrophic sea fans, while VEGF immunoreactivity was weak or absent in these structures. In conclusion, PEDF and VEGF were both significantly elevated in viable sea fan formations in sickle cell disease ( p<0·05) but only PEDF was present in non-viable sea fans. The highest levels of PEDF in all eyes were associated with extracellular matrices (vitreous, choroidal stroma, IPM, and walls of blood vessels). PEDF might play an important role in inhibiting angiogenesis and inducing the regression of sea fans. Progression of angiogenesis may be dependent on the ratio of PEDF/VEGF.

Initial Experience with the Utility of Infrared Diode Laser in Kaduna, Nigeria

Our initial clinical experience with the use of a diode laser in the treatment of some retinovascular conditions and refractory glaucoma in some black patients in Kaduna, Nigeria. Methods: All the 32 eyes of 26 patients treated with diode laser photocoagulation between September 1997 and September 1999, were studied retrospectively. Patient's eye, sex, eye diagnosis. laser treatment parameters and the intra-operative and post-operative observations were tabulated. Results: All patients tolerated the laser treatment sessions, although complaints of pain were universal. The follow up observation period ranged from none to one year in this initial study. Eight of 6 patients were treated for proliferative sickle cell retinopathy. Regression of sea fans was observed in all the four eyes (100%) of three patients that were available for follow-up observation. However, a fresh sea-fan neo-vascularisation developed elsewhere in the same retina of one of the treated eyes. Of the 12 eyes of 9 patients with diabetic retinopathy, 6 patients (8eyes) were available for follow up. Among the later group, all eyes but one (87.5%) had their retinopathy changes stabilised following laser treatment. Two patients with central retina vein occlusion were treated. The only one that was available for follow up was stabilized following treatment. Of the 3 eyes (3 patients) that had retinopexy for flat retina breaks, 2 reported for follow up. Both retina remained attached. All the 6 patients (7 eyes) with refractory glaucoma who contact diode laser treatment did not have the initial reduction in the intra-ocular pressures sustained subsequently. Conclusion: Diode laser has been found to be useful in treating a number of retinovascular conditions among the black patients studied. Its initial intra-ocular pressure lowering effect was not sustained in refractory glaucoma. However, the small pool of patients and the limited period of follow up examination in this study call for caution with these conclusion. KEY WORDS: Diode laser treatment, sickle cell retinopathy, diabetic retinopathy, retinopexy refractory glaucoma [Nig. J. Ophthalmology Vol.10(1): 37-44]

Trans-scleral diode laser photocoagulation in proliferative sickle cell retinopathy

Objective To demonstrate the feasibility of trans-scleral diode laser photocoagulation for the treatment of proliferative sickle cell retinopathy. Design Interventional case report. Intervention Trans-scleral diode laser scatter photocoagulation was applied to both eyes of a 30-year-old man with hemoglobin SC disease. Main outcome measures Regression of retinal vascular proliferation and of dye leakage on fluorescein angiography. Results After coagulation, vascular proliferation receded completely. Vitreous bleeding was absorbed. There were no side effects during follow-up (22 months). Conclusion Trans-scleral diode laser photocoagulation proved to be an effective and safe treatment in a case of proliferative sickle cell retinopathy with vitreous bleeding.

Angiogenic factors in human proliferative sickle cell retinopathy

BACKGROUND/AIMSPreretinal neovascular formations called sea fans develop at the border of non-perfused peripheral retina in sickle cell retinopathy. Angiogenic factors which could contribute to their development, however, have not been...

Histopathologic Features of Neovascularization in Sickle Cell Retinopathy

To examine the histopathologic and morphometric features of neovascular lesions in human proliferative sickle cell retinopathy. 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. 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. 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.

Evolution of a Retinal Hemorrhage in a Patient With Sickle Cell-Hemoglobin C Disease

In1987, during a cross-sectional survey of patients with sickle cell disease on the island of Curacao, 1 I documented a salmonpatch retinal hemorrhage in a 17-year-old black man with sickle cell-hemoglobin C disease. Part of the retinal hemorrhage had broken through into the vitreous; the intraretinal part of the hemorrhage was hemolyzed and pink. This hemorrhage originated from the (whitish) arteriole ( Figure 1 and Figure 2 ). During a follow-up visit in 1993, the hemorrhage had evolved into a black-sunburst chorioretinal scar ( Figure 3 and Figure 4 ). COMMENT Sight-threatening complications in patients with sickle cell disease almost invariably arise from proliferative sickle cell retinopathy, which occurs mainly in patients with sickle cell-hemoglobin C disease or hemoglobin S-β-thalassemia. The majority of patients with homozygous sickle cell disease, sickle cell-hemoglobin C disease, or sickle cell-β-thalassemia, however, show sequelae of retinal hemorrhages that fortunately rarely affect vision. Hannon 2 coined the term salmon-pink

Recent advances in the treatment of proliferative sickle cell retinopathy.

Sickle cell eye disease is characterized by microvascular occlusion that affects the peripheral retinal vasculature and results in retinal ischemia and the development of proliferative sickle cell retinopathy. Complications of proliferative sickle cell retinopathy such as vitreous hemorrhage and retinal detachment are the most common causes of visual loss in this disease. Prevention of this visual loss is therefore contingent on the prevention or early detection and treatment of proliferative sickle cell retinopathy. Most effort has been directed toward therapy for established proliferative sickle cell retinopathy, and several therapeutic trials have been reported. Much less is known about the risk factors for development of proliferative sickle cell retinopathy and its natural history, in particular the true incidence of permanent visual loss. Visual loss is believed to be predominantly a complication of perfused proliferative sickle cell retinopathy, and its autoinfarction renders such visual loss less likely. To better define the place of treatment, identification of the determinants of autoinfarction is required, but identification of patients whose proliferative sickle cell retinopathy is likely to proceed to visual loss is of greater importance.

An update on techniques of photocoagulation treatment of proliferative sickle cell retinopathy

Proliferative sickle cell retinopathy (PSR) can lead to visual loss from vitreous haemorrhage and traction or rhegmatogenous retinal detachment. We review two techniques of photocoagulation for PSR, feeder vessel photocoagulation and scatter photocoagulation. A prospective randomised trial of feeder vessel photocoagulation for PSR demonstrated that the incidence of vitreous haemorrhage and visual loss was diminished in eyes which were treated. Since this technique of treatment is difficult and can be associated with choroidal neovascularisation and retinal tears, scatter photocoagulation has also been tested. A prospective randomised trial of scatter photocoagulation for PSR demonstrated a decreased incidence of vitreous haemorrhage and visual loss in treated eyes compared to untreated eyes. No complications of scatter treatment were noted. We presently recommend local scatter photocoagulation to areas of PSR. In unreliable patients, we recommend 360 degrees of peripheral circumferential treatment as otherwise new seafans will develop. If scatter photocoagulation does not result in sufficient regression of the neovascularisation and vision threatening complications such as vitreous haemorrhage continue, feeder vessel treatment can be used to supplement the scatter treatment.

A Randomized Clinical Trial of Scatter Photocoagulation of Proliferative Sickle Cell Retinopathy

A randomized prospective clinical trial of argon laser scatter photocoagulation therapy for proliferative sickle cell retinopathy was performed on 116 patients (174 eyes) in Kingston, Jamaica. Ninety-nine eyes were treated with scatter photocoagulation and 75 eyes served as controls. The average length of follow-up was 42 months for the control eyes and 47 months for the treated eyes. Prolonged loss of visual acuity was statistically significantly reduced in the treated eyes. The incidence of vitreous hemorrhage was also significantly reduced in the treated eyes after controlling for the previously defined risk factors of vitreous hemorrhage and extent of proliferative sickle cell retinopathy at entry into the study. There were no complications associated with argon laser scatter photocoagulation. Scatter photocoagulation of proliferative sickle cell retinopathy is currently the most effective and safe way to treat patients with sea fan neovascularization.

Peripheral Multifield Scanning Fluorescein Angiography for the Evaluation of Proliferative Sickle Cell Retinopathy

Evaluation of proliferative sickle cell retinopathy requires detailed studies of the retina periphery, including pre-treatment documentation of active neovascular (sea fan) lesions. Multifield angiography of the periphery (MAP) is recommended for the analysis of these lesions. This method is also valuable for the pre- and post-treatment quantitative angiographic evaluation of peripheral circumferential retinal scatter photocoagulation (PCRP).

Proliferative Sickle Cell Retinopathy: The Disease and a Review of its Management

Proliferative Sickle Cell Retinopathy: The Disease and a Review of its Management

Proliferative Sickle Cell Retinopathy Under Age 20: A Review

Of the 256 sickle patients with hemaglobinopathies SC, SS and S-thal referred to the Wills Eye Hospital Retina Vascular Service from 1966 through 1983, 64 (50%) of the 128 males and 71 (55%) of the 128 females were less than 20 years old. Proliferative sickle retinopathy (PSR) was documented by fluorescein angiography in five of the males (8%) and two of the females (3%) under age 20. Included in this series is a 13-year-old black girl with homozygous sickle cell anemia (HbSS), to our knowledge the youngest reported case of PSR in an SS patient. This report emphasizes the importance of ophthalmic examinations in teenage sickle patients to detect and treat proliferative disease.