Symptomatic abnormalities of dark adaptation in patients with EFEMP1 retinal dystrophy (Malattia Leventinese/Doyne honeycomb retinal dystrophy).

PURPOSE: To investigate the nature of symptomatic visual disturbance in patients with EFEMP1 retinal dystrophy in the absence of geographic atrophy or choroidal neovascularization. METHODS: Patients presenting to a tertiary referral centre underwent clinical evaluation, fluorescein angiography, colour contrast sensitivity, focal, pattern, and standard electroretinography, electrooculography, scotopic threshold perimetry and dark adaptometry. RESULTS: Clinical features included reduced central vision, difficulty passing from light to dark, and diffuse submacular and peripapillary deposits, which were hyperfluorescent by fluorescein angiography. Colour contrast thresholds were abnormal in all six patients studied and both pattern and focal electroretinograms were abnormal in five of six patients. The scotopic and mixed rod-cone single flash ERG was normal but two patients demonstrated reduced oscillatory potentials and one had borderline delayed 30 Hz responses. Scotopic thresholds were elevated and rod-mediated dark adaptation kinetics were markedly prolonged in all six patients when measured over the central visible confluent deposits. CONCLUSIONS: In patients with EFEMP1 retinal dystrophy with confluent macular deposits, scotopic sensitivity is reduced and dark adaptation kinetics are prolonged over the macular deposits but are normal elsewhere. These results emphasize the localised nature of functional deficits in some patients with EFEMP1 retinal dystrophy and correlate well with the patient's visual symptoms. Symptomatic visual dysfunction may precede the development of clinically evident geographic atrophy or choroidal neovascularization in this disorder.

The lipid composition of drusen, Bruch's membrane, and sclera by hot stage polarizing light microscopy.

PURPOSE: To detect and identify, in situ, the lipid composition of drusen, diffuse Bruch's membrane deposits, and sclera in aging human eyes using hot-stage polarizing microscopy (HSPM), a method that allows qualitative determination of lipid subtypes within histologic sections based on morphology and melting temperatures of liquid crystals as monitored by birefringence during heating and cooling. METHODS: Full-thickness buttons of the central macula and the periphery of human eyes from 17 patients were fixed in 5% calcium-buffered formalin. Frozen sections were stained with oil red O or Sudan black or were analyzed by HSPM. RESULTS: Birefringent anisotropic droplets ("maltese crosses") with melting characteristics of cholesterol esters were identified within diffuse Bruch's membrane deposits, drusen, and sclera. Deposits that melted from crystal to oil without any maltese cross formation when cooled were present in the sclera and are consistent with triglyceride-rich deposits. Deposits with optical properties consistent with phospholipids were identified in a single aged eye. Eyes from young donors did not show these changes. CONCLUSIONS: HSPM is a valuable technique for evaluating the nature of lipid deposits in aging eyes. Further studies are warranted to determine whether similar changes are also present in eyes with age-related macular degeneration.

Corneal biopsy in the management of progressive microbial keratitis.

PURPOSE: To study the indications and role of diagnostic corneal biopsy in the management of patients with progressive microbial keratitis. METHODS: The records of 33 consecutive patients who underwent a diagnostic corneal biopsy from January 1, 1986, to December 31, 1998, were reviewed. The indication for corneal biopsy was progressive infectious keratitis despite intensive broad-spectrum topical antimicrobial therapy, or progressive stromal infiltration inaccessible to corneal scrapings. Microbiologic evaluation of all corneal biopsies was performed, and 11 of the 33 biopsies were also examined histopathologically. RESULTS: A microorganism was isolated from 27 (82%) of the 33 corneal biopsies. Of the six patients with a negative biopsy, a penetrating keratoplasty was performed in five patients and the pathogen was identified by examination of the corneal button. In one patient no microorganism was identified; however, the infection resolved with topical antimicrobial therapy. The most common risk factor for keratitis was foreign body exposure or corneal abrasion (14 patients). A solid stromal infiltrate was the most common pattern of corneal involvement. Corneal biopsy revealed previously unidentified microorganisms that led to a change in antimicrobial therapy in 24 (89%) of the 27 patients and confirmed prior culture results in the remaining 3 patients. Microbiologic evaluation of the corneal biopsy was more sensitive than histopathologic examination. Acanthamoeba was the most commonly isolated pathogen (five cases), followed by Propionibacterium acnes and Fusarium (four cases each). Gram-positive organisms were isolated in 16 patients. Only five of the 27 patients with a positive corneal biopsy required a penetrating keratoplasty, in contrast to five of the six patients with a negative corneal biopsy (P =.005). During the 13-year period of the study, only three corneal biopsies were performed in the last 6 years. CONCLUSIONS: Microbiologic evaluation of a diagnostic corneal biopsy contributed significantly to the diagnosis, treatment, and outcome of patients with progressive infectious keratitis.

Silicone oil emulsification of the retinal surface.

A 35-year-old patient with cytomegalovirus (CMV) retinitis secondary to acquired immunodeficiency syndrome (AIDS) underwent pars plana vitrectomy and fluid-gas-silicone exchange for retinal detachment. Three weeks following surgery and additional laser photocoagulation, extensive retinal surface emulsification was noted. It masked the retinal surface and demonstrated shifting in subsequent examinations. This case stresses the importance of careful and close follow-up after pars plana vitrectomy and silicone oil injection. Silicone oil emulsification may in some cases require removal of the emulsified fluid or silicone oil exchange, but in others such as our case, shifting of the emulsified silicone oil may allow evaluation of the nonobscured retina.

Management of retained intravitreal lens fragments after cataract surgery.

With the rise of popularity of phacoemulsification as the preferred surgical method for cataract extraction, there has been an increased incidence of posterior dislocation of lens fragments. The appropriate management of this complication both during and after cataract extraction is discussed in this review. It is suggested that vigorous attempts by the cataract surgeon to retrieve intravitreal lens fragments should be avoided. Timely referral to a posterior segment surgeon for pars plana vitrectomy and removal of lens fragments can result in good visual outcome. Complications, such as glaucoma and retinal detachment, may develop in some cases. The importance of careful clinical follow-up is emphasized.

Central serous chorioretinopathy associated with inhaled or intranasal corticosteroids.

OBJECTIVE: The purpose of the study is to investigate the relationship between inhaled or intranasal adrenergic agonists and corticosteroids and the development of central serous chorioretinopathy (CSC). DESIGN: The medical records of three patients with CSC who were found to use inhaled adrenergic agents or corticosteroids or both were identified prospectively. A survey of members of the Retina, Macula, and Vitreous societies and the National Registry of Drug-Induced Ocular Side Effects identified three additional cases. RESULTS: Six patients with CSC were found to be chronic users of corticosteroid (four patients) or both beta adrenergic agonist and corticosteroid (two patients) metered dose inhalers or nasal sprays. In three cases, there was a close temporal correlation between the use of a corticosteroid nasal spray and the development of CSC. CONCLUSIONS: These findings suggest that, in patients who are susceptible, the periocular or systemic absorption of inhaled corticosteroids may be sufficient to produce CSC in humans, supporting previous hypotheses regarding the pathogenesis of the disorder. Further studies are needed to confirm this association and to determine whether inhaled adrenergic agents also contribute to the development of this disorder. Patients in whom CSC develops while using corticosteroid inhalers or nasal sprays should be alerted to the possible relationship between CSC and these agents.

Choroidal metastases from renal cell carcinoma.

BACKGROUND: Choroidal metastases from renal cell carcinoma are uncommon. The authors investigated the clinical characteristics of patients with renal cell carcinoma in whom choroidal metastases developed. METHODS: The clinical records of five patients with histopathologically confirmed renal cell carcinoma and choroidal metastases were reviewed retrospectively. RESULTS: In four patients, choroidal metastases were either the sole initial manifestation of disease or were the initial manifestation of metastatic disease. The interval from nephrectomy to the onset of ocular signs ranged from 6 to 18 years. A reddish-orange appearance of the tumor was present in two patients, but no pathognomonic features distinguishing these tumors from other choroidal metastases were identified. CONCLUSIONS: Ocular metastases may precede the diagnosis of renal cell carcinoma or may follow it by years or decades. This interval between its ocular and systemic presentation may be so prolonged as to obscure the relation between the choroidal metastases and the primary tumor. In patients with amelanotic or reddish choroidal lesions without known metastatic disease, evaluation of the kidney may be warranted as part of a metastatic workup to exclude metastatic renal cell carcinoma.

Localization of lipoprotein-delivered benzoporphyrin derivative in the rabbit eye.

PURPOSE: Photodynamic therapy (PDT) using the photosensitizer Benzoporphyrin derivative monoacid (BPD-MA or verteporfin) is currently under investigation for the treatment of choroidal neovascularization. We investigated the localization of this photosensitizer using fluorescence microscopy and quantified its presence in ocular tissues after porphyrin extraction using fluorescence spectroscopy. METHODS: Albino rabbits were administered 2mg/kg BPD-MA pre-complexed with low density lipoprotein (LDL) intravenously, or given no treatment. The eyes were enucleated at intervals between 5 minutes and 24 hours after dye injection and were studied with light and fluorescence microscopy, or dissected for porphyrin extraction. RESULTS: At 5 minutes after dye injection, there was bright fluorescence from the choroid and retinal pigment epithelium (RPE) with trace retinal outer segment fluorescence. After 20 minutes, there was increased photoreceptor outer segment and RPE fluorescence but decreased choroidal fluorescence. By 2 hours no fluorescence remained in either the choroid or the photoreceptors and there was diminished fluorescence of the RPE. Trace RPE fluorescence was still visible at 24 hours. Fluorescence localization of liposomal BPD (2mg/kg) at the earliest (5 minutes) time point was indistinguishable from that of the BPD-LDL complex. Using spectrofluorimetry, the highest BPD-MA levels from the eye were measured in the retina/RPE/uvea complex with lower levels measured from the sclera and other tissues. CONCLUSIONS: BPD-MA with LDL rapidly accumulates in the choroid, RPE, and photoreceptors after intravenous injection. Future studies of PDT with BPD-MA for the treatment of fundus disorders may need to address the relationship between dye localization and photodynamically-mediated injury.

Intravitreal toxicity of dental adhesives in the rabbit.

PURPOSE: The authors tested the intravitreal toxicity of four commonly employed dental adhesives to determine their suitability as retinal adhesives. METHODS: Two glass ionomers, a polycarboxylate, and a composite resin (Ketac-Bond Radiopaque Poly Maleic Acid [ESPE, Oberbay, Germany], Vitrebond Light Cure Glass Ionomer [3M, St. Paul, MN], Carbchem Zinc Polycarboxylate Cement [PSP Dental Company, Kent, United Kingdom], and Kerr Porcelite Dual Cure [Kerr, Romulus, MI]) were reconstituted according to the manufacturer's recommendations, and 0.1 mliter was injected separately into the vitreous cavity of New Zealand white rabbits. Serial slit-lamp and funduscopic evaluations were performed up to 3 months after injection. Selected eyes were studied angiographically and histopathologically. RESULTS: Intravitreal administration of the glass ionomers Ketac-bond or Vitrebond lead to intense vitritis within the first weeks. Necrotic retinal detachments ultimately developed in these eyes, along with those administered the polycarboxylate cement Carbchem. Eyes injected with the composite resin Porcelite Dual Cure showed no ophthalmoscopic evidence of vitreous or retinal toxicity and no angiographic evidence of vascular toxicity. Histopathology of the eyes with this intravitreal composite resin cement revealed mild disorganization of photoreceptor nuclei and outer segments. CONCLUSIONS: Among the agents studied, the dual-cure composite resin cement Porcelite showed the least ocular toxicity. Further studies to evaluate its intraocular toxicity and efficacy as a retinal adhesive are warranted.

Rhegmatogenous retinal detachment in eyes with uveal melanoma.

PURPOSE: To describe the clinical features, surgical management, and outcome of patients with uveal melanoma who presented with or later developed a rhegmatogenous retinal detachment. METHODS: We retrospectively identified four patients who presented with uveal melanoma and rhegmatogenous retinal detachment simultaneously and six patients in whom a rhegmatogenous retinal detachment developed 11-100 months (mean, 44.8 months) after radiotherapy for a choroidal melanoma. RESULTS: All four patients with simultaneous presentation of uveal melanoma and retinal detachment underwent successful retinal detachment repair (cases 1 and 4, scleral buckle; case 2, pars plana vitrectomy, and case 3, pneumatic retinoplexy). Rhegmatogenous retinal detachment occurring after proton beam or plaque radiotherapy of uveal melanoma was repaired successfully in five of six patients with scleral buckling alone or in combination with pars plana vitrectomy. In the short follow-up period of this study, we did not observe tumor recurrence either before or after retinal detachment repair. CONCLUSION: Rhegmatogenous retinal detachment associated with uveal melanoma may be treated successfully using conventional retinal surgical techniques. The benefits of retinal detachment repair must be weighed against any theoretical increased risk of extra-scleral extension of the melanoma. Long-term follow-up evaluation will be required to determine the safety of various retinal detachment repair techniques in these eyes.

Advances in vitreoretinal surgery: macular hole repair and perfluorocarbon liquids.

1. Idiopathic macular hole was once thought to be an untreatable disorder. During the past several years, surgical techniques have evolved that allow for closure of the macular hole, with restoration of vision in many cases. 2. Perfluorocarbon liquids are an important class of compounds that are under investigation for use in vitreoretinal surgery. The use of these compounds facilitates the performance of intraocular surgical maneuvers in certain difficult-to-manage vitreoretinal disorders. These substances have a high specific gravity and are able to displace water within the eye, facilitating reattachment of the retina in certain types of retinal detachments such as those associated with proliferative vitreoretinopathy and giant retinal tears. PFCLs also aid in the removal of intravitreal lens fragments or foreign bodies and in the repositioning or removal of dislocated intraocular lenses. 3. Ophthalmic nurses and technicians can play an important role in initial screening for these patients. Detection of symptoms may lead to early diagnosis of idiopathic macular hole and subsequent treatment. Patient education emphasizing topics such as the importance of strict postoperative face-down head positioning may be critical for successful surgery.

Photodynamic therapy of experimental choroidal neovascularization using lipoprotein-delivered benzoporphyrin.

OBJECTIVE: To investigate photodynamic therapy of experimental choroidal neovascularization using benzoporphyrin derivative monoacid (Verteporfin). METHODS: Photodynamic therapy using benzoporphyrin derivative monoacid was investigated in cynomolgus monkeys. Following intravenous injection of benzoporphyrin derivative monoacid (1 to 2 mg/kg) complexed with low-density lipoprotein, the eyes were irradiated with 692-nm light at a fluence of 50 to 150 J/cm2 and irradiance of 150 to 600 mW/cm2. Choroidal neovascularization was documented before photodynamic therapy and closure was demonstrated by fundus photography, fluorescein angiography, and light and electron microscopic examination. RESULTS: Following photodynamic therapy, vessels within choroidal neovascularization were occluded, and there was damage to the choroidal neovascularization endothelium and the subjacent choriocapillaris. Damage to the retinal pigment epithelium and photoreceptors was also observed. CONCLUSION: Photodynamic therapy with lipoprotein-delivered benzoporphyrin derivative monoacid was effective in this animal model of choroidal neovascularization and may be a promising, potentially selective, therapy for choroidal neovascularization.

Dominantly inherited drusen represent more than one disorder: a historical review.

Hutchinson-Tay choroiditis, Holthouse-Batten chorioretinitis, Doyne's honeycomb familial choroiditis and Malattia levantinese are various names which have been used to denote dominantly inherited drusen. Whether these represent one or more than one disorder remains unclear because of the quality of the illustrations and incomplete information in some of the original articles. The early descriptions of these various conditions have been reviewed. Evidence is presented that Doyne's honeycomb familial choroiditis and Malattia levantinese are disorders which can be distinguished from each other by clinical criteria.

Recurrent choroidal neovascularization after laser photocoagulation in Sorsby's fundus dystrophy.

BACKGROUND: Patients with autosomal dominant Sorsby's fundus dystrophy are at high risk of severe visual loss due to choroidal neovascularization (CNV) during the fourth or fifth decade of life. METHODS: To assess the efficacy of argon laser photocoagulation for extrafoveal well-defined CNV, we analyzed retrospectively the clinical course in 10 eyes of 7 patients who had Sorsby's fundus dystrophy with CNV 200 microns to 2,500 microns from the center of the foveal avascular zone, and who subsequently underwent laser photocoagulation. RESULTS: All treated eyes developed severe visual loss as a consequence of recurrent or persistent CNV occurring on the foveal side of the treatment scar, which extended under the fovea. The average time until occurrence of angiographically documented CNV after initial treatment was 8.1 +/- 8.9 weeks, but ranged from 2 weeks to 32 weeks. Retreatment for persistent or recurrent extrafoveal CNV was performed in 5 eyes, but CNV recurred in all 5. CONCLUSIONS: Results of this study suggest that the risk of persistence or recurrence of CNV after laser photocoagulation for extrafoveal CNV is unusually high in patients with Sorsby's fundus dystrophy, and that this treatment is ineffective in preventing severe visual loss in such patients.

Symptomatic abnormalities of dark adaptation in patients with age-related Bruch's membrane change.

Some patients with age-related changes at the level of Bruch's membrane and good visual acuity report poor vision in dim light, fading vision in bright light, and a central scotoma noticeable in the dark. Ophthalmic examination, scotopic thresholds, and dark adaptation kinetics were recorded in 12 eyes of 12 patients with such symptoms. All had macular drusen which were hypofluorescent on fluorescein angiography in nine subjects, and six had evidence of prolonged choroidal filling on fluorescein angiography. Scotopic thresholds were depressed in six patients who all experienced a central scotoma in the dark or poor night vision. The kinetics of dark adaptation were abnormal in all 10 patients in whom reliable measurements were possible. The findings suggest that visual symptoms reflect abnormality of both scotopic sensitivity and the time course of dark adaptation in patients with age-related Bruch's membrane change.

Suprachoroidal hemorrhage. Clinical features and results of secondary surgical management.

PURPOSE: The purposes of this study are to identify clinical features in eyes with suprachoroidal hemorrhage which portend a poor visual prognosis and to determine visual outcome in these eyes after secondary surgical management of suprachoroidal hemorrhage. METHODS: This was a retrospective study of 106 patients with suprachoroidal hemorrhages occurring in association with trauma (35), cataract surgery (30), glaucoma surgery (17), penetrating keratoplasty (6), corneal perforation (5), secondary lens implantation (3), pars plana vitrectomy (3), and other causes (7). RESULTS: Five (10%) of 49 eyes with a suprachoroidal hemorrhage and an initial retinal detachment had a visual outcome of 20/200 or better compared with 21 (43%) of 49 eyes without a retinal detachment. The presence or absence or a retinal detachment could not be determined in eight patients and all eight of these patients had a poor visual outcome. Sixteen (20%) of 82 eyes with a 360 degrees suprachoroidal hemorrhage had a visual outcome of 20/200 or better compared with 10 (47%) of 21 for those with suprachoroidal hemorrhage limited to one or two quadrants. The extent of the hemorrhage could not be determined in three eyes. Overall, 34% (14/41) of the patients with suprachoroidal hemorrhage who had a secondary surgical procedure achieved a visual outcome of 20/200 or better. Forty-three percent (6/14) who had a suprachoroidal hemorrhage during or after cataract surgery and who were treated with secondary surgical management achieved a visual outcome of 20/200 or greater. CONCLUSION: Clinical features associated with a poorer visual outcome included initial or indeterminate retinal detachment and 360 degrees suprachoroidal hemorrhage. Limited suprachoroidal hemorrhage without initial retinal detachment usually has a good visual prognosis and does not usually require secondary surgical intervention. However, if the former complication is present, secondary surgical intervention should be considered.

Paracentral rheumatoid corneal ulceration. Clinical features and cyclosporine therapy.

Six patients with rheumatoid arthritis (eight eyes) presented with small paracentral perforating corneal ulcers in otherwise quiet eyes. Initial management in five patients (seven eyes) consisted of systemic immunosuppression and therapeutic tissue adhesive with a bandage contact lens or tectonic keratoplasty. Ulceration recurred in all of these eyes, and recurrent ulcers treated with repeat tectonic keratoplasty or therapeutic tissue adhesive and a bandage contact lens all developed recurrent ulceration. The introduction of topical cyclosporine therapy in five eyes with recurrent corneal ulceration was associated with arrest of keratolysis and rapid re-epithelialization of the ulcer in all cases. One corneal ulcer was successfully treated initially with topical cyclosporine, tissue adhesive, and a bandage contact lens. In patients with rheumatoid arthritis and small paracentral corneal ulcerations or perforations, application of tissue adhesive and a bandage contact lens and introduction of topical cyclosporine may be the preferred initial treatment.