Retinal Opacification Research Articles

Congenital Retinal Dystrophy and Corneal Opacity in Trisomy 8 Mosaicism

Trisomy 8 mosaicism can present with a wide variety of systemic and ophthalmologic manifestations. We report a patient with an extinguished electroretinogram and diffuse retinal pigment epithelial abnormalities suggestive of a rod-cone dystrophy, which has not been previously reported in association with trisomy 8. A finding that has been described in several patients with trisomy 8 is a central corneal opacity, but there are no data regarding the natural history of this finding; the corneal opacity in our patient spontaneously improved. This case expands the clinical spectrum of this rare entity.

PROGRESSIVE OUTER RETINAL NECROSIS CAUSED BY VARICELLA-ZOSTER VIRUS IN CHILDREN WITH ACQUIRED IMMUNODEFICIENCY SYNDROME

We report three HIV-infected children with bilateral progressive outer retinal necrosis caused by varicella-zoster virus. All three lost vision in both eyes. Aggressive treatment strategies with combination intravenous antiviral therapy in addition to intravitreal antiviral therapy and appropriate surgical management may prevent blindness. Rapid recognition of this distinct clinical syndrome is essential to improve visual outcome.

Persistent scotomata after improvement of visual acuity in patients with cilioretinal artery occlusion

To evaluate changes in scotomata and visual acuity in patients with cilioretinal artery occlusion, we examined 1 patient with an associated central retinal vein occlusion and 2 with isolated cilioretinal artery occlusion. All patients underwent ophthalmic examination, including visual acuity, fundus photography, fluorescein angiography, and Humphrey perimetry tested for at least 6 months. Despite improvement in visual acuity and disappearance of retinal opacification after 1 month, scotomata remained 3 months after the initial examination.

Acute annular outer retinopathy: report of four cases

PURPOSE: To describe the clinical findings and course in four patients with acute annular outer retinopathy. METHODS: Four patients were evaluated during the course of acute annular outer retinopathy, and the historical and clinical findings were retrospectively collected. RESULTS: Four healthy patients developed the acute onset of visual field loss associated with a localized, white annular outer retinopathy. All patients were caucasian; two were women, aged 29 and 32 years, and two were men, aged 71 and 79 years. The mean follow-up was 3.9 years (range, 1 to 6 years). On presentation, four eyes had an irregular, incomplete, peripapillary, annular band of gray-white, deep retinal opacification with visual acuities that varied from 20/25 without foveal involvement to counting fingers with foveal involvement. Laboratory serologies were unremarkable. Two patients did not receive any treatment, and two received varying courses of oral corticosteroids with subjective improvement. Of the four eyes, two eyes developed ophthalmoscopic sequelae, one eye did not, and one had evidence of retinal pigment epithelial damage and narrowing of the retinal vessels on presentation. CONCLUSIONS: These four cases of acute annular outer retinopathy expand our knowledge of this disorder. Acute annular outer retinopathy may be a distinct entity or it may represent a variant of acute zonal occult outer retinopathy. As more cases are recognized, the characteristic features of the disease spectrum, the etiology, and treatment options may be better elucidated.

Tamoxifen retinopathy: does it really exist?

Tamoxifen retinopathy is known to be an adverse effect of high-dose tamoxifen treatment. Evidence of ocular toxicity at lower doses is less convincing: the aim of this study was to assess the prevalence of the above-mentioned retinopathy in a population treated with low-dose tamoxifen. One hundred and twenty-nine women treated with low-dose tamoxifen (20 mg/day) were examined. Visual acuity measurement, slit-lamp biomicroscopy and fundus examination were performed. Patients were reexamined after 6-12 months. Refractile retinal opacities, similar to those previously described as tamoxifen retinopathy, were observed in four patients (prevalence 3.1%; mean duration of therapy 806 days). None of them revealed corneal opacities, papillary and/or macular edema, or visual impairment. The ophthalmoscopic aspect did not change after a mean follow-up of 215 days, although one of these patients had interrupted tamoxifen intake. Statistical analysis (Student's t-test) did not reveal any difference between patients with and those without refractile retinal opacities as far as age, treatment duration and ERG values were concerned. An early hyperfluorescence, reminescent of cuticular drusen, was demonstrated by fluorescein angiography in all four cases. The present study would seem to confirm that low-dose tamoxifen may induce retinal toxicity in a low proportion of patients, but we cannot be certain that the refractile retinal opacities observed are really caused by tamoxifen, as differentiation from age-related macular degeneration with cuticular drusen appears nearly impossible.

Choroidopathy after blunt trauma to the eye: a fluorescein and indocyanine green angiographic study

PURPOSE: To describe the uses of fluorescein angiography and indocyanine green angiography in highlighting traumatic choroidopathy. METHODS: In a prospective study, 21 patients (21 eyes) who presented with traumatic retinal opacity ophthalmoscopically underwent fluorescein angiography and indocyanine green angiography. With indocyanine green angiography, the subtraction method was used for detailed examination. RESULTS: In 11 of 21 eyes, fluorescein angiography showed no abnormalities. On indocyanine green angiography, delayed filling in the choroid was found locally in nine of these 11 eyes. Delayed filling of the choroidal veins was clearly visualized by the subtraction method. In six eyes, intrachoroidal indocyanine green leakage around the choroidal vessels, including vortex veins, was found. In the remaining 10 of the 21 eyes, fluorescein angiography showed fluorescein leakage or a salt-and-pepper appearance in the region of retinal opacity. On indocyanine green angiography, a triangular-shaped area of delayed filling of the choroidal arteries was observed in four eyes. Delayed filling of the choroidal veins was visualized in all 10 eyes, intrachoroidal indocyanine green leakage was found in eight, and dilation and/or narrowing of the choroidal veins and changes in choroidal vasculature were visualized in five eyes. Furthermore, in regions with fluorescein leakage, indocyanine green leakage or hypofluorescence was observed, suggesting damage to the choriocapillaris. CONCLUSION: Indocyanine green angiography allows the analysis of various degrees of choroidal vascular damage. Because the choroidal circulation nourishes the outer retinal layer, traumatic choroidopathy may play a role in the prognosis for visual recovery in eyes affected by contusion retinal opacities.

Retinal and choroidal manifestations of cat-scratch disease

Objective The ability to diagnose cat-scratch disease (CSD) has been facilitated greatly by the recent isolation and characterization of Bartonella henselae (formerly genus Rochalimaea) and Afipia felis and by the subsequent development of specific enzyme-linked immunosorbent assay (ELISA) serologic tests. This study will help define the patterns of posterior segment ocular involvement in patients with confirmed CSD. Design The study design is a retrospective case study and literature review. Participants Two consecutive patients with acute visual loss from retinal manifestations of CSD participated. Interventions The diagnosis was confirmed by B. henselae ELISA testing. Patients underwent extensive medical and ophthalmic investigations to exclude other causes of retinal and choroidal disease. Ophthalmic investigation included fluorescein angiography and visual field testing. One patient received antibiotic therapy with cefotaxime, then with ciprofloxacin, and was treated with oral prednisone. The other patient was improving for several weeks before oral doxycycline was given. Main outcome measures The clinical syndromes observed were studied over time using visual acuity, visual field, and clinical findings. Data were collated with cases from the literature. Results Unilateral neuroretinitis and an unusual macular retinitis developed in patient 1, as did bilateral small intraretinal white spots and a unilateral choroidal infiltrate that continued to develop while the patient received antibiotic treatment. Patient 2 had a branch arteriolar occlusion in relation to a perivascular retinal infiltrate and a few small, bilateral, intraretinal white spots. There was gradual resolution with visual improvement while the patient received the antibiotic treatment, although therapeutic efficacy could not be determined. Patient 1 also received oral corticosteroids. A detailed analysis of the literature placed these findings in context. Conclusions An unusual, well-defined retinal opacification with features of both multiple retinal arteriolar occlusions and a low-grade retinitis was described. Several features also may occur in posterior segment CSD, including neuroretinitis, a retinal white spot syndrome, and focal choroiditis.

Photographic and angiographic characterization of the retina of Kenyan children with severe malaria.

To investigate retinal lesions in children with severe falciparum malaria. Color photography and fluorescein angiography were performed in consecutive children admitted to a pediatric high-dependency unit in Kenya during 1 malaria season. The presence and category of retinal lesion was compared with disease severity, clinical outcome, anemia, lactic acidosis, and parasite count. Twenty-six patients with cerebral malaria and 14 patients who were prostrate were studied. Thirty-one of the patients had clinical features of ocular disease, including round, flame-shaped, and white-centered hemorrhages; peripheral and foveal retinal opacification; peripheral vascular occlusion; venous dilation; disc edema with hyperemia; and arterial pulsatility. Of 8 patients with retinal opacification, only 2 showed small, infrequent zones of capillary nonperfusion on fluorescein angiography; the leakage of dye at sites of opacification was not seen. Retinal opacification was significantly associated with a higher parasite count (P < .02). White-centered hemorrhages were significantly associated with a higher parasite count (P < .05), severe disease (p < .05), and severe anemia (P < .02). The blood-retina barrier and retinal vascular flow remain substantially normal despite widespread pathological features. Retinal features in children with severe malaria are consistent with cellular hypoxia, nutritional deficiency, or both rather than with vascular occlusion; they support the concept of metabolic steal by parasites.

Treatment of cytomegalovirus retinitis with intravitreous cidofovir in patients with AIDS. A preliminary report.

Cytomegalovirus retinitis remains a major cause of illness in patients with the acquired immunodeficiency syndrome (AIDS), and existing therapies for this condition are relatively ineffective and toxic. To evaluate the efficacy of intravitreous cidofovir injections alone for initial and maintenance therapy for cytomegalovirus retinitis. Prospective, nonrandomized, consecutive case series. University ophthalmology referral clinic. 22 patients with AIDS and cytomegalovirus retinitis. In 15 of 32 affected eyes, intravitreous cidofovir was administered as the initial treatment for cytomegalovirus retinitis (group A); 17 eyes had previously been treated with intravenous therapy (group B). All eyes were intravitreously injected with 20 micrograms of cidofovir at 5- to 6-week intervals. No patient in either group received systemic anticytomegalovirus therapy at any time during the study period. Healing of retinitis was defined as resolution of retinal opacification and cessation of border progression. Progression, the primary end point, was defined as 750 microns of border progression or development of a new lesion. The mean duration of follow-up was 15.3 weeks (range, 5 to 44 weeks). Of the eyes with active retinitis, 100% (95% CI, 87% to 100%) healed in response to the initial injection. In two eyes (6%; CI, 0% to 15%), two episodes of retinitis progression occurred (one in each eye). Both of these eyes were in a patient with clinically resistant retinitis. In 3% of eyes (CI, 0% to 9%), the retina became detached. Mild iritis developed after 14% of the injections that had been preceded by prophylaxis with oral probenecid. Irreversible, visually significant hypotonia developed in one eye. Treatment and subsequent maintenance of cytomegalovirus retinitis with 20 micrograms of intravitreously injected cidofovir, given at 5- to 6-week intervals, is safe and highly effective.

Ocular Toxoplasmosis Misdiagnosed as Cytomegalovirus Retinopathy in Immunocompromised Patients

Cytomegalovirus (CMV) and Toxoplasma gondii both cause necrotizing retinopathy in immunosuppressed hosts. Because of the high prevalence of serum antibodies to these agents in the general population and the risks associated with retinal biopsies, diagnosis of these infections is usually based on clinical findings alone, but the two infections can be confused with one another because of similar clinical features. Accurate diagnosis is critical, however, because both diseases are treatable but require different medical therapies. Case histories were reviewed for five immunosuppressed patients with necrotizing retinopathy, which was initially diagnosed incorrectly as CMV retinopathy but was subsequently found to be toxoplasmic retinochoroiditis. Correct diagnosis was based on retinal biopsy (2 cases) or rapid response to antiparasitic drug therapy (3 cases). Factors were sought that might help differentiate toxoplasmic retinochoroiditis from CMV retinopathy at presentation. In all cases, the character of retinal opacification (densely opaque, thick) and the appearance of lesion borders (smooth, nongranular) was different from that typically seen with CMV retinopathy. These cases also were characterized by prominent anterior chamber and vitreous inflammatory reactions (four of five cases) and relative lack of retinal hemorrhage. One patient subsequently developed CMV retinopathy; characteristics of the two lesions in the same eye highlighted the differences between these two infections. Clinicians should consider ocular toxoplasmosis as a cause of necrotizing retinopathy in immunosuppressed patients and consider an empiric course of antiparasitic therapy for lesions with features described in this report.

The progressive outer retinal necrosis syndrome.

The progressive outer retinal necrosis (PORN) syndrome is a recently described clinical variant of necrotizing herpetic retinopathy in patients with the acquired immunodeficiency syndrome (AIDS). It is caused by varicellazoster virus infection of the retina. Its course and clinical features distinguish it from the acute retinal necrosis syndrome and CMV retinopathy. Early disease is characterized by multifocal deep retinal opacification. Lesions rapidly coalesce and progress to total retinal necrosis over a short period of time. Despite aggressive therapy with intravenous antivirial drugs, prognosis is poor; disease progression and/or recurrence is common, and the majority of patients develop no light perception vision. Total retinal detachments are common. Prophylaxis against retinal detachment using laser retinopexy has not been useful in most cases. PORN syndrome is an uncommon, but devastating complication of AIDS.

Recurrence of Presumed Varicella-zoster Virus Retinopathy in Patients with Acquired Immunodeficiency Syndrome

Five patients with acquired immunodeficiency syndrome (AIDS) and presumed varicella-zoster virus retinopathy had recurrence of retinopathy after stabilization with initial intravenous antiviral therapy. Recurrences were recognized as increased retinal opacification at the borders of preexisting lesions or as new lesions. In four of the five patients, recurrences were temporally associated with a reduction in the amount of antiviral medication being received. Changes included switch from intravenous to oral acyclovir (two patients), taper of oral acyclovir (one patient), and discontinuation of medications (one patient). In four patients disease was initially unilateral; in three of these four, disease subsequently developed in the previously unaffected fellow eye at the time of recurrence. The median time from stabilization of disease to recurrence was 51 days (range, 14 to 90 days). In contrast to the management of varicella-zoster virus retinopathy in immunocompetent patients and varicella-zoster virus lesions of the skin, varicella-zoster virus retinopathy in patients with AIDS appears to require chronic suppressive antiviral therapy to prevent recurrences. In this respect it is similar to other opportunistic retinal infections in patients with AIDS. The best drugs and optimal treatment regimens for maintenance antiviral therapy remain unknown.

An animal model of focal, subacute, viral retinitis.

To study local intravitreal therapies for retinitis due to herpes viruses, an animal model of focal, subacute, relatively nonlethal herpes family retinitis is needed. Herpes simplex virus type 1 (HSV-1) was injected into the subretinal space of 33 Dutch pigmented rabbit eyes. The animals were observed for up to 42 days after the inoculation. All inoculated eyes developed a focal, enlarging area of retinitis in a predictable manner, showing focal enlarging areas of retinal opacification and necrosis with variable retinal hemorrhage. In the inoculated eyes, retinal detachment developed in all animals within 21 days; 33% of the animals developed focal retinitis in the uninoculated eye. Histologic examination showed encephalitis to be present in 11 (73%) of the 15 animals studied after 1 week. This model may be used to evaluate the therapeutic efficacy of new antiviral agents and modalities in the treatment of herpes family viral retinitis. The model is most similar to herpes simplex or zoster retinitis in humans, but also shares some similarities (and differences) with cytomegalovirus (CMV) retinitis in humans.

Clear evidence that long-term, low-dose tamoxifen treatment can induce ocular toxicity. A prospective study of 63 patients.

The current study has prospectively investigated the incidence and course of ocular toxicity after low-dose tamoxifen treatment. Sixty-three patients with cancer who could be examined were analyzed. Tamoxifen was administered on a 20-mg daily dose. Median duration of treatment was 25 months. Median total tamoxifen dose was 14.4 gr. Four patients had retinopathy and/or keratopathy 10, 27, 31, and 35 months, respectively, after tamoxifen initiation (an incidence of 6.3%). Ophthalmologic findings consisted of decreased visual acuity, bilateral macular edema, yellow-white dots in the paramacular and fovea areas in all patients as well as corneal opacities in one patient. After tamoxifen withdrawal almost all ocular abnormalities were found to be reversible, except for the retinal opacities. This is the first prospective study in the literature indicating that even conventional low-dose tamoxifen treatment can induce ocular toxicity. In addition, the authors review and discuss the literature of the last decades.

Intrachoroidal dye leakage in indocyanine green fundus angiography after experimental commotio retinae.

Dye leakage in sodium fluorescein (FLUO) fundus angiography indicates damage to the blood-retinal barrier. However, dye leakage in indocyanine green (ICG) fundus angiography does not mean the same, because of the larger molecular size of the dye and impermeability of the choroidal vessels to it. The possibility of dye leakage in ICG angiography has not yet been revealed in an experimental study in which the blood-retinal barrier is undamaged. We report here that intrachoroidal dye leakage may occur in ICG angiography in an experimental model of the traumatic retinal opacity of the rabbit eye, even when the blood-retinal barrier is undamaged. This mechanism of dye leakage in ICG angiography is quite different from the leakage of FLUO angiography. Pathological choroidal vessels with increased permeability, such as choroidal neovascularization under the retinal pigment epithelium, can be observed using ICG angiography.

Retinal Artery Obstruction and Atheromas Associated With Non-Hodgkin's Large Cell Lymphoma (Reticulum Cell Sarcoma)

A 71-year-old woman developed branch retinal artery obstruction as the presenting manifestation of a large cell non-Hodgkin's lymphoma. Multifocal chorioretinal scars were present in the same eye. She experienced progressive visual loss accompanied by development of multiple yellow retinal arterial wall plaques, extension of retinal opacification into other quadrants, and increasing vitreous cellular infiltration. Clinical diagnoses included branch retinal arterial obstruction caused by toxoplasmosis retinitis, multifocal choroiditis and panuveitis simulating the presumed ocular histoplasmosis syndrome, vitiliginous chorioretinitis, and the acute retinal necrosis syndrome. Four months after onset, the right eye was blind and was enucleated. Histopathologic examination revealed extensive lymphomatous infiltration and necrosis of the retina and optic nerve. The retinal arteries were partly obstructed by lymphomatous infiltration and atheromas. Subsequently, the left eye and central nervous system were involved by lymphoma.

Retinopathy of prematurity: approaches to surgical therapy

Retinopathy of prematurity (ROP) is a vasoproliferative disease with infiltration of the vitreous gel. Contraction of the infiltrate results in traction detachment with typical peripheral trough formation. Cryotherapy inhibits proliferation in the active stages of the disease (Stage 3, 'plus'). With development of traction detachment involving the macula (Stage 4B) encircling buckling procedures should first be tried. Closed vitrectomy is considered when high retinal detachment and opacification by vitreous strands occur. The surgical technique is described. Anatomical (64%) and functional (43%) successes are reasonably high for Stage 4 cases, but disappointing (anatomical 40%, functional 16%) for Stage 5 ROP. Open funnels of detached retina fare better than closed ones. It is probably best to perform surgery not before the cicatricial stage, i.e. six months after birth.

A Controlled Retrospective Study of Ganciclovir Treatment for Cytomegalovirus Retinopathy

To evaluate more accurately the clinical response of cytomegalovirus retinopathy to ganciclovir, a system for the assessment of disease outcome was developed that uses retinal photographs and three factors: development of new lesions, enlargement of preexisting lesions, and change in retinal opacification of lesion borders. With this system a retrospective comparison was performed of 24 ganciclovir-treated patients and 17 untreated patients with cytomegalovirus retinopathy. A masked assessment showed disease progression in 10 treated patients (43%) during a median period of 22 days. In contrast, 16 untreated patients (94%) had progression of disease during a median period of 25 days. Comparison of treated and untreated eyes also suggests that treatment may prevent deterioration of visual acuity during the same period. This study supports the conclusions of previous uncontrolled studies that ganciclovir is beneficial in the treatment of patients with acquired immunodeficiency syndrome and cytomegalovirus retinopathy. It also demonstrates the utility of the proposed system for assessment of disease outcome that can be used in future studies of therapy for necrotizing viral retinopathies.

Foscarnet treatment of cytomegalovirus retinitis in patients with the acquired immunodeficiency syndrome

Ten patients with acquired immunodeficiency syndrome with newly diagnosed cytomegalovirus (CMV) retinitis were treated with an induction regimen of intravenous foscarnet, 60 mg/kg of body weight, administered as a 2-h infusion and repeated every 8 h for 14 days. At the end of induction, 9 of 10 patients had stabilized (no new retinal lesions and stable old lesions [7 patients]) or improved (decreased retinal opacification [2 patients]). All eight patients with CMV in urine or blood upon entry into the study had negative urine and blood cultures at the end of induction. After induction therapy, seven patients continued maintenance foscarnet therapy, 60 mg/kg as a single daily infusion, 5 days/week. In six patients, retinal lesions increased in size after 2 to 32 weeks of maintenance therapy. One was invaluable because a retinal detachment developed. Only 9 of 42 blood and urine cultures obtained during maintenance foscarnet therapy yielded CMV, compared with 7 of 14 obtained prior to the initiation of foscarnet induction therapy (P = 0.04). Foscarnet toxicity was mild and infrequent: elevation in serum creatinine by 0.5 to 1.3 mg/dl over the base line (two patients), muscle twitching (three patients), hemoglobin decrease by 1 mg/dl (two patients), nausea (two patients), absolute neutrophil count decrease by 50% (one patient), rise in serum phosphorus to greater than 5.5 mg/dl (four patients), and proteinuria (two patients). Intermittently administered intravenous foscarnet appears to be an effective, relatively nontoxic therapy for CMV retinitis. Additional studies to determine the optimal dosage for maintenance therapy are needed, as are comparative trials with ganciclovir.

Treatment of cytomegalovirus retinopathy in patients with acquired immunodeficiency syndrome. Use of the experimental drug 9-[2-hydroxy-1-(hydroxymethyl)ethoxymethyl]guanine.

Cytomegalovirus (CMV) retinopathy, a relentlessly progressive disease that results in permanent blindness, is the most common opportunistic infection of the eye in patients with the acquired immunodeficiency syndrome. Twenty patients with the acquired immunodeficiency syndrome with CMV retinopathy were treated with a new, experimental, antiviral drug, 9-[2-hydroxy-1-(hydroxymethyl)ethoxymethyl]guanine (BW B759U), in dosages ranging from 5.0 to 14.0 mg/kg/d for a ten- to 20-day course. In 19 patients (95%), treatment halted the progression of infection and decreased retinal opacification, hemorrhage, and vasculitis. Vision remained stable in most cases. Six patients received no additional treatment. Fourteen patients received continued treatment with a lower maintenance dosage. Retinal disease reactivated in all patients who did not receive maintenance therapy immediately after initial treatment, indicating persistence of live virus despite drug therapy. Reactivation of disease also developed in four (40%) of ten patients receiving continuous, uninterrupted maintenance therapy for longer than three weeks. Reversible neutropenia, requiring cessation of treatment, developed in five (25%) of 20 patients on initial treatment and five (36%) of 14 patients receiving maintenance therapy. Rhegmatogenous retinal detachment was a late complication in four patients. BW B759U appears to be useful in the management of CMV retinopathy by reducing or delaying visual loss.