Laser biospectroscopy and 5-ALA fluorescence navigation as a helpful tool in the meningioma resection.

5-aminolevulinic acid (5-ALA) is a natural precursor of protoporphyrin IX (PP IX), which possesses fluorescent properties and is more intensively accumulated in tumor cells than in normal tissue. Therefore, the use of 5-ALA in the surgical treatment of intracranial tumors, particularly gliomas, has gained popularity in the last years, whereas its use in other intracranial pathological entities including meningiomas has been reported occasionally. This study describes a series of 28 patients with intracranial meningiomas, who were administered 5-ALA for a better visualization of tumor boundaries. Twelve patients underwent also laser spectroscopic analysis in order to confirm the visual impression of tumor tissue visualization. Bone infiltration was readily demonstrated. In one case, the tumor recurrence could have been prevented by removal of a tumor remnant, which would possibly have been better recognized if spectroscopic analysis had been used. Fluorescent navigation (FN) is a useful method for maximizing the radicality of meningioma surgery, particularly if the tumor infiltrates the bone, the skull base, and/or the surrounding structures.

Developmental abnormalities in the Nuc1 rat retina: a spontaneous mutation that affects neuronal and vascular remodeling and retinal function.

The retina serves as an excellent model in which to study vertebrate CNS development. We have discovered a spontaneous mutation in the Sprague-Dawley rat that results in a novel and unusual ocular phenotype, including retinal abnormalities, that we have named Nuc1. We have previously shown that the Nuc1 mutation appears to suppress programmed cell death in the developing retina. Here we report that maturation of both the retinal neurons and the retinal vessels is abnormal in Nuc1 homozygous rats. The developmental changes in the retinal neurons and vasculature are correlated with regard to degree of abnormality. As Nuc1 homozygotes mature, focal retinal detachment begins at approximately 3 months after birth, and near total traction retinal detachment, associated with pre-retinal fibrosis and neovascularization, is evident by 18 months. Electroretinographic studies at 2.5 months of age indicate that functional retinal degeneration precedes retinal detachment. The functional abnormality is most evident in rods and the inner retina, and is present in homozygous but not heterozygous mutants. Immunocytochemical studies of rod and cone photoreceptors indicate abnormalities in rod, but not cone, photoreceptors in Nuc1 homozygotes, consistent with the electroretinographic findings. In Nuc1 animals, the Muller cells are activated. Although such activation may result from inflammation, Muller cells in Nuc1 may be reacting to a neuronal influence. It appears that the Nuc1 mutation plays a regulatory role in both developing and maturing ocular tissues. The Nuc1 mutation may also serve as an important genetic tool to explore the relationships that may exist among gliosis, normal neuronal development, and normal vascular development and how abnormalities in these associations lead to common retinal diseases.

Proliferative retinopathy in sickle cell trait. Report of seven cases.

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.

Noninvasive visualization of blood flow in the choriocapillaris of the rat.

PURPOSE: The rat has been used to generate models of various eye diseases. However, methods to study the choriocapillaris noninvasively have been inadequate in this species. Laser-targeted angiography was applied to generate local, repetitive angiograms of the choriocapillaris in the rat and to assess the similarity between the choriocapillaris of the rat and that of the subhuman primate. METHODS: Carboxyfluorescein was encapsulated in heat-sensitive liposomes and injected intravenously in rats. The liposome contents were then released locally in the choroid by the application of a short, noncoagulating heat pulse provided by an argon laser. Videoangiograms of the downstream spread of the bolus of dye were generated with excitation illumination provided by another output from the argon laser. RESULTS: Laser-targeted angiography demonstrated that the bolus of dye perfused the choriocapillaris. Clusters of choriocapillaris lobules were observed and appeared similar to those described in the primate. Dynamic filling and emptying patterns also were similar to those of the primate. Lobules were filled by a central arteriole and drained by a venous annulus. CONCLUSIONS: This study demonstrates the feasibility of noninvasively studying the choriocapillaris of the living rat using the technique of laser-targeted angiography. It demonstrates as well the similarity between the rat and the primate choriocapillaris, thus indicating that the rat is an acceptable and convenient model for the study of physiological and pathologic changes in the choroidal vasculature.

The use of hyperbaric oxygen therapy in the treatment of sickle cell hyphema.

Eyes of adult albino rabbits were injected intracamerally with either normal saline or anticoagulated human sickle cell blood to study the effect of hyperbaric oxygen administration on sickle cell hyphema. The administration of two atmospheres of 100% oxygen for 2 hr to the rabbits raised the pO2 of the aqueous humor from a baseline value of 63.5 +/- 12.3 mmHg (mean +/- SD) to 620 +/- 133 mmHg in saline-injected eyes and 503.7 +/- 89.1 mmHg in eyes injected with human sickle cell blood. This rise in pO2 was highly significant (P less than 0.0001). The percentage of sickled cells in the anterior chamber 2 hr after injection decreased from 35.7 +/- 32.4% in rabbits breathing room air to 4.1 +/- 2.8% in rabbits exposed to hyperbaric oxygen for 2 hr. Hyperbaric oxygen can thus significantly raise aqueous humor pO2 values and decrease the sickling of erythrocytes in the anterior chamber and may be of value in patients with sickle cell hyphema.

Feasibility of laser-targeted photoocclusion of the choriocapillary layer in rats.

PURPOSE: A new method, laser-targeted photoocclusion, was developed to occlude choroidal neovascularization while minimizing damage to the overlying retina. The ability to occlude normal choriocapillary layer in rats was evaluated as a first test of the feasibility of treating choroidal neovascularization with this method. METHOD: A photosensitive agent, aluminum phthalocyanine tetrasulfonate, encapsulated in heat-sensitive liposomes, was administered intravenously along with carboxyfluorescein liposomes. A low-power argon laser (retinal power density of 5.7 W/cm2) locally released a photosensitizer bolus, monitored by the simultaneous release of carboxyfluorescein. A diode laser (operating at 675 nm with a retinal power density of 0.27 W/cm2) activated the photosensitizer with its release. RESULTS: Vessels in the choriocapillary layer were occluded at day 3 after laser treatment and remained unchanged during the 30-day follow-up. Larger choroidal vessels and retinal capillaries remained perfused. Control experiments excluded possible effects of heat or activation of free photosensitizer. Pilot histologic studies showed no damage to the retinal pigment epithelium. CONCLUSIONS: Laser-targeted photoocclusion caused selective occlusion of normal choriocapillaries while sparing overlying retinal pigment epithelium and retinal vessels. The method has potential as a treatment of choroidal neovascularization that may minimize iatrogenic loss of vision.

Retinal breaks after photocoagulation of proliferative sickle cell retinopathy.

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 angiographic pattern of the peripheral retinal vasculature.

Various diseases of the peripheral retinal vasculature, such as sickle cell retinopathy and Eales' disease, demonstrate vascular abnormalities. For comparative purposes, we documented angiographically the peripheral retinal vasculature in young, healthy subjects. Our findings showed the density of the capillary bed to be highest in the posterior pole and least concentrated toward the periphery. Peripheral capillaries are considerably larger than those found posteriorly and have fewer bifurcations. Our technique also detected the periarterial capillary-free zone and the zone without capillaries adjacent to the ora serrata. These aspects were consistent with findings of other investigators using in vitro techniques. By creating a standard of normalcy in vivo, the angiographic technique allows vascular abnormalities evident in diseases of the peripheral retinal vasculature to be more precisely defined and compared.

Retinal periarteritis secondary to syphilis.

A 43-year-old black woman showed ophthalmoscopic evidence of retinal arteriolitis two weeks after being treated for uniocular panuveitis. Angiographic examination suggested that these deposits were not intraluminal or endothelial atherosclerotic emboli or plaques, but were deposits in the outer walls of retinal arterioles. Sequential ophthalmoscopic and angiographic examinations at one-month intervals for 12 months showed no progression or change in location of these deposits. Results of clinical and laboratory investigations suggested the diagnosis of syphilis. We believe it is rare for syphilitic infection to be implicated in the diagnosis of isolated retinal arteriolitis without periphlebitis.

Identification of a nonsense mutation at codon 128 of the Norrie's disease gene in a male infant.

OBJECTIVE: Norrie's disease (ND) is a rare X-linked hereditary disorder characterized by congenital blindness. A putative gene for ND has been isolated and mapped to Xp11.3. Four point mutations in this gene have been identified recently in patients with ND, thus providing strong evidence that this gene is associated with the disease. We report a new mutation. DESIGN: Clinical findings from the proband were correlated with results from DNA analysis. The proband's DNA was compared with that from his mother, an unaffected brother, and four unrelated normal males. PATIENT: The proband was a male infant referred for ocular evaluation at 3 months of age. INTERVENTIONS: The patient was evaluated with a general ocular examination at 4 months of age, a computed tomographic scan at 8 months of age, and then periodic follow-up examinations over the next 7 years. Blood samples were also collected from the proband, his family, and four unrelated normal males. DNA was extracted, amplified using polymerase chain reactions, and then cloned and sequenced. RESULTS/CONCLUSIONS: We identified a new mutation at codon 128 of the ND gene, a dinucleotide GC-to-AA substitution that changed the normal codon for cysteine, TGC, to TAA, which is a stop codon. Thus, this patient lacks the last six amino acids of the carboxyl terminus of the ND protein. The normal ND protein has 11 cysteines in conserved positions that are proposed to be functionally significant. The mutation at codon 128 occurs at the 10th cysteine and might be expected to alter the function of the ND protein. Since the phenotype of this patient is similar to those of other patients with point mutations in the ND gene, this mutation is likely to be the molecular basis of the phenotype.

Laser-induced chorioretinal venous anastomosis for nonischemic central or branch retinal vein occlusion.

OBJECTIVE: To establish a communication between an obstructed retinal vein and the choroid by means of laser in eyes with nonischemic central or branch vein occlusion. METHODS: Retrospective review identified eyes with nonischemic central or branch vein occlusion, and with decreasing or persistently decreased visual acuity of 20/100 or worse for 4 months or more before treatment, that received 1 or more sessions of laser photocoagulation to create a chorioretinal anastomosis. RESULTS: Of 24 eyes with central vein occlusion, an anastomosis formed in 9 (38%) within 2 months after treatment, with visual improvement of 6 or more lines in 2 (8%) of 24 eyes, 1 to 3 lines in 5 (21%), and no improvement in 2 (8%). Of 6 eyes with branch vein occlusion, an anastomosis formed in 3 (50%) within 2 months after treatment, with visual improvement of 1 to 3 lines in 2 (33%) of 6 and no improvement in 1 (16%). No permanent, vision-limiting complications occurred during a mean follow-up of 13 months after the first treatment session or 8 months after the last session. CONCLUSIONS: Laser photocoagulation of a retinal vein and Bruch's membrane may create a chorioretinal anastomosis in some eyes with a nonischemic vein occlusion. Progression to an ischemic status may possibly be prevented with successful anastomosis formation. Marked visual improvement may occur. Treatment techniques to create reliably an anastomosis with subsequent visual improvement, while minimizing potential complications, continue to evolve.

Optic disc neovascularization of uveal (choroidal or posterior ciliary) origin.

Fluorescein angiography during the choroidal phase of perfusion has been used to study the origin of blood vessels comprising neovascular tissue of the disc. These newly formed vessels were shown to derive their blood supply primarily from the uveal circulation rather than from the retinal circulation. This is related to the observation that many normal disc blood vessels originate from the choroidal or posterior ciliary circulation.

Argon laser-induced cataract. A clinicopathologic study.

A patient with diabetic retinopathy and senile anterior cortical and nuclear cataract was treated with argon laser photocoagulation of the fundus. During the treatment, white ovoid opacities appeared in the lens cortex, extending into the nucleus. They remained nonprogressive for five weeks, when cataract extraction was performed. The lens was studied by light and electron microscopy. The lenticular opacities contained rows of damaged, spindle-shaped lens fibers, with laminated cellular debris and clear spaces. We compared the unique features of the laser-induced lenticular lesions with the senile cataractous changes in the same crystalline lens.

Pilot trial of transscleral diode laser retinopexy in retinal detachment surgery.

OBJECTIVE: To evaluate the safety and efficacy of the transscleral diode laser for retinopexy in rhegmatogenous retinal detachments. DESIGN: Ten consecutive patients with primary rhegmatogenous retinal detachments underwent scleral buckling surgery, using the transscleral diode laser for retinopexy. Patients were followed up for at least 6 months. STUDY PARTICIPANTS: Ten patients with primary rhegmatogenous retinal detachments were enrolled. Patients with chronic detachments, a retinal break greater than 90 degrees, history of uveitis or infectious retinopathy, or proliferative vitreoretinopathy were excluded. MAIN OUTCOME MEASURE: Retinal reattachment. Secondary measures: visual acuity and complications, including choroidal, retinal, and vitreous hemorrhage, inflammation, and scleral damage. RESULTS: By 6 months, nine of 10 retinas were successfully repaired following only one operation. The retina of the 10th patient redetached at 6 1/2 weeks owing to proliferative vitreoretinopathy. Following a vitrectomy and retinal reattachment procedure, the retina of the 10th patient has remained attached for 1 year. No significant complications were encountered with the laser retinopexy, although small presumed breaks in Bruch's membrane occurred in three eyes and a moderate scleral thermal effect occurred in two. Visual results in the postoperative course were comparable to those achieved previously with cryotherapy. CONCLUSION: In this pilot series, transscleral diode laser retinopexy served as a safe and effective means of obtaining chorioretinal adhesion in retinal detachment surgery.

Dual-perspective analysis of vascular formations in sickle cell retinopathy.

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.

Peripheral retinal neovascularization in sarcoidosis.

Three black patients with peripheral retinal sea fan neovascularization were found to have sarcoidosis. The periphlebitic process may be the cause of stasis, hypoxia, and a secondary vasoproliferative stimulus. We noted the peculiar finding of a vessel passing through the neovascular tissue into the peripheral retina. This feature may help in the differential diagnosis.

Indications for surgical management of hyphema in patients with sickle cell trait.

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.

Chorioretinal and choriovitreal neovascularization. Their presence after photocoagulation of proliferative sickle cell retinopathy.

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.

Traumatic hyphema in children: risk factors for complications.

OBJECTIVE: To identify risk factors associated with higher rates of ocular complications in children with traumatic hyphema. METHODS: Consecutive inpatient records from July 1990 through December 1997 were retrospectively reviewed for all children (aged < or = 18 years) who were admitted to the Wilmer Ophthalmological Institute, Baltimore, Md, within 48 hours of a closed-globe injury leading to hyphema. Data obtained included age, sex, race, sickle cell status, initial and final visual acuities, hyphema size and intraocular pressure at presentation, the occurrence of a secondary hemorrhage, subsequent intraocular pressure elevations, and therapeutic interventions. RESULTS: Forty children fulfilled the inclusion criteria: 20 African American, 1 Asian American, and 19 white. Five of the 20 African American children had sickle cell trait, and 1 had sickle cell anemia. The rate of secondary hemorrhage was statistically higher in the African American population (P =.05), but no statistical difference existed between the rate of secondary hemorrhage in patients with and without sickle cell hemoglobinopathy. Sickle cell hemoglobinopathy was associated with a higher intraocular pressure at presentation (P =.03) and during inpatient follow-up (P =.02). CONCLUSIONS: In the setting of traumatic hyphema, African American children appear to be at greater risk for developing a secondary hemorrhage. In our patients, sickle cell hemoglobinopathy increased the risk of intraocular pressure elevation, but did not seem to increase the risk of rebleeding beyond that associated with race. Larger studies are needed to validate these observations.

Retinal macroaneurysms.

Five patients had macroaneurysms of the retinal arterioles. These macroaneurysms may be observed without pathologic sequelae or may be associated with circinate retinopathy, intraretinal hemorrhage, subretinal hemorrhage, or intravitreal hemorrhage. They may also evolve into more widespread vascular anomalies resembling adult Coats disease in some respects. Photocoagulation therapy is occasionally indicated.