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Purpose: To review emerging information related to changing concepts in the management of choroidal melanoma., Design and Methods: This perspective reviews and discusses selected studies from the past two decades that have influenced management strategies for large, medium, and small-size choroidal melanomas., Results: Large choroidal tumors continue to be managed primarily by enucleation. The large tumor trial of the Collaborative Ocular Melanoma Study (COMS) demonstrated neither a positive nor negative effect on 5- and 8-year mortality rates among more than 1000 patients whose eyes containing large choroidal melanomas were randomized to treatment between enucleation alone or enucleation preceded by external radiation. The medium-size tumor trial of the COMS randomized more than 1300 patients between iodine-125 brachytherapy and enucleation. Mortality rates following brachytherapy did not differ from mortality rates following enucleation for up to 12 years after treatment. Iodine-125 has become the most commonly used isotope for brachytherapy in North America. Ten-year follow-up of eyes treated with helium ion and 20 years of experience with proton beam confirm the relative safety and efficacy of these modalities for treatment of choroidal melanoma. Although there is a trend toward earlier treatment of small melanomas, controversy exists regarding the indications for treatment as well as the choice of specific therapy. Recurrences of melanoma after eye-sparing treatment appear to be associated with an increased rate of metastatic disease. Effective adjunctive therapy to prevent or treat melanoma metastasis is lacking., Conclusions: Choroidal melanoma is a lethal tumor. Although evidence suggests that patients with untreated choroidal melanomas have a poorer prognosis than patients who receive treatment, our current treatments are unable to prevent tumor-related deaths for many patients. The use of preoperative external radiation as an adjunct to enucleation for large choroidal melanomas is unsupported by data from the COMS trial. The use of radiation with either brachytherapy or charged particles for the management of medium-size choroidal melanomas is well supported on the basis of long-term follow-up studies. There is a trend toward treatment of smaller choroidal melanomas. Treatment of melanomas should be directed toward minimizing the potential for recurrences as recurrent melanomas are associated with an increased rate of metastatic disease. Gains in our ability to manage choroidal melanoma will likely be modest at best until effective systemic therapies can be identified.

The population of the western world is ageing. This increase in the elderly population will inevitably mean a rise in the prevalence of age-related cognitive decline and late-onset neuropsychiatric disorder, such as Alzheimer's disease (AD). There are sex differences in the incidence and age of onset of these disorders. Sex steroids and sex chromosomes are therefore implicated in their pathophysiology. We have identified relevant past and current literature using a Medline search and from the references of relevant papers. These were then reviewed and relevant articles have been summarized and included in the review. Evidence is presented for the wide-ranging actions of estrogen in the brain at the cellular, metabolic and neurotransmitter levels as well as from the cognitive, AD, depression and cerebrovascular perspectives. The authors conclude that it is unlikely that estrogen will become a stand-alone treatment for any of these disorders, although there may still be a role as an adjunctive treatment and as a prophylactic measure.

This survey reviews selected medical disorders in which the ophthalmologist has a unique opportunity of anticipating the existence of asymptomatic, life-threatening disease simply by recognizing that certain benign conditions involving the eye or adnexa represent clues to occult non-ocular cancer and other neoplasias. Having knowledge that these clues are associated with specific types of neoplasia, the ophthalmologist can then initiate a goal-directed oncologic investigation designed to identify the underlying neoplasm with the hope of providing potentially life-saving therapy. The survey is organized to feature each clue separately. The clinical characteristics of the clue are described and illustrated with color photographs when possible. A discussion reviews associated malignancies and other important medical features. The survey begins with clues expressed anteriorly in the lids, progressively reviewing those clues located more posteriorly, concluding with clues involving the retinal pigment epithelium and choroid.

Purpose: The principal objectives of this study were to estimate the incidence of second tumors among children treated for heritable retinoblastoma during a 50-year period and to investigate the relationship between these tumors and previous radiation therapy., Methods: The records of all retinoblastoma patients examined at the Mayo Clinic from 1941 through 1990 were retrospectively reviewed. The therapeutic modality used to manage the tumor, the occurrence of any second malignancy, and current follow-up on all patients were evaluated., Results: Eighty-two (46%) of 180 children with retinoblastoma had bilateral tumors (76 patients) or unilateral disease and a positive family history (six patients) and were followed for an average of 21.8 years (range, 1 month to 53 years). The Kaplan-Meier estimates of second nonocular tumors among the 82 patients with heritable retinoblastoma were 12% at 10 years, 16% at 25 years, and 30% at 40 years. Although 14 of the 15 patients who developed second malignancies had received radiation therapy, only four of the malignancies occurred within the field of irradiation., Conclusions: The relatively low incidence of second tumors among long-term survivors of heritable retinoblastoma in this series of patients occurred predominantly outside the field of irradiation. The variable incidence of second nonocular malignancies in previous reports may reflect variations in radiation technique and dosage.

Purpose: To obtain long-term photographic follow-up of retinal astrocytic hamartomas in patients with tuberous sclerosis to learn about their stability or possible growth patterns., Methods: Sixteen patients with a confirmed diagnosis of tuberous sclerosis and in whom retinal astrocytic hamartomas were photographed before 1986 at the Mayo Clinic underwent a complete ophthalmic examination, and fundus photographs were taken. The new photographs were compared with previous photographs, and changes in size, character, or number of retinal hamartomas were determined. The minimum follow-up period was five years., Results: A total of 37 astrocytic hamartomas were found. Follow-up ranged from almost six years to more than 34 years, with an average of 16 years. Hamartomas in three patients showed progressive or new calcification. In a fourth patient a retinal hamartoma appeared to originate from a site that had been previously photographically documented to be normal. The remaining hamartomas appeared unchanged over the follow-up period., Conclusions: Although most retinal lesions in tuberous sclerosis remain stable, some become calcified over time. Additionally, new lesions may develop from previously normal-appearing retina.

Purpose/methods: We observed a clinicopathologic correlation of a case of adenocarcinoma of the retinal pigment epithelium., Results/conclusions: The ultrasonographic findings of this tumor demonstrated a collar button profile with high internal reflectivity. The ultrasonographic characteristics in this case reflected the variable vascularity and cystic spaces within the tumor.

Purpose: The primary objective of this study was to determine whether ancillary testing for metastasis is justified in the routine examination of patients with newly diagnosed retinoblastoma., Methods: The records of all patients with retinoblastoma diagnosed at the Mayo Clinic from 1952 through 1989 or examined within two months of diagnosis elsewhere were reviewed. The ancillary tests used to detect metastatic disease, available histopathologic specimens, and five-year follow-up were recorded on all patients., Results: We identified 100 patients, with newly diagnosed retinoblastoma, who were ultimately followed up for at least five years after diagnosis or until death. Of the 100 patients, 35 underwent bone marrow aspiration, lumbar puncture, or both, within one month of diagnosis. Results of all ancillary tests performed in these 35 patients were negative for metastatic disease. Nine of the 35 patients had choroidal extension and two had retrolaminar involvement. Although one patient developed orbital recurrence that was successfully treated with exenteration and chemotherapy, none of the 35 patients died of metastatic retinoblastoma in a mean follow-up period of 9 1/2 years. The overall survival free of metastasis from retinoblastoma in these 100 patients was 97% at five years (95% confidence interval: 94% to 100%)., Conclusions: The routine use of bone marrow and lumbar puncture studies in the examination of all patients with newly diagnosed retinoblastoma cannot be supported by this study.

Two patients with massive epithelium-lined inclusion cysts of the orbit became symptomatic five and 16 years after scleral buckling. Each patient described diplopia and displacement of the previously treated eye. An orbitotomy in the first patient disclosed a loculated epithelium-lined inclusion cyst that extended posteriorly from the insertion of the inferior rectus muscle nearly to the apex of the orbit. In the second patient, a loculated epithelium-lined inclusion cyst extended into the superior nasal portion of the orbit from its origin near the insertions of the superior and medial recti muscles. We speculated that epithelial cells of the conjunctiva were shed at the time of scleral buckling and became lodged in the exposed sulcus created by the surgical retraction of Tenon's capsule. Here they proliferated and formed the large epithelium-lined cysts. In each patient, removal of the cyst was followed by a decrease in diplopia as the displaced globe returned toward its normal position.

The macular retina of a patient whose eye was scheduled for enucleation because of progressive growth of a malignant melanoma that had invaded the iris and filtration angle was exposed to unfiltered light from the operating-room microscope for 60 minutes. Photic maculopathy was documented with fundus photography and fluorescein angiography 67 hours after light exposure. Seventy-two hours after light exposure, the eye was enucleated, fixed in Trumpe's solution, and studied with light microscopy and electron microscopy. Findings included localized necrosis of the retinal pigment epithelium; loss of the apical villi, plasma membranes, and cytoplasmic organelles; extrusion of pigment granules; and extensive disruption of the outer lamellae of the photoreceptors. The inner segments of the photoreceptors were edematous and contained swollen mitochondria. Near the margins of the photic retinopathy, thinned retinal pigment epithelial cells appeared to have migrated under injured retinal pigment epithelial cells, suggesting early attempts at repair. Additional findings included Müller-cell swelling.

We reviewed the records of 22 patients (22 eyes) who had presumed small choroidal melanomas associated with a serous macular detachment. In 13 eyes, the tumor surface was treated with laser photocoagulation to reattach the retina and improve vision. After photocoagulation, the retina reattached in 11 eyes (85%), and the visual acuity improved in eight eyes (62%), returning to 20/25 or better in six eyes (46%). Twelve of the tumors (92%) that received surface photocoagulation grew after treatment. Seven of these tumors (54%) developed a collar-button configuration and showed evidence of basal expansion. Of the nine tumors that did not receive surface photocoagulation, seven (78%) eventually grew, but none developed a collar-button configuration. Surface photocoagulation applied to a growing melanoma appears to increase the likelihood of tumor extension through Bruch's membrane in a collar-button configuration. The impact of such growth on tumor metastasis is unknown.

We analyzed a total of 473 eyes with rhegmatogenous retinal detachment and macular involvement for significant factors relating to anatomic success and a favorable visual outcome of 6/15 (20/50) or better. The overall success rate was 90% (427 of 473 eyes). Visual acuities of 6/15 (20/50) or better postoperatively were present in 37% (174 of 470 eyes). Important factors related to both anatomic success and favorable functional results were preoperative visual acuities of 6/15 (20/50) or better, retinal detachments that were less than total, detachments with tears located at or anterior to the equator, absence of giant retinal tears, absence of either preoperative ocular hypotony (tension less than 5 mm Hg) or ocular hypertension (intraocular pressure greater than 20 mm Hg), detachments managed by nondrainage techniques, a single operation with less than 50 cryoapplications, and noncircumferential buckling. Among the other factors related to favorable visual results were detachments lasting less than one month, a shallowly rather than highly detached macula, the absence of fixed retinal folds, a patient age of less than 60 years, and the absence of postoperative choroidal detachments sufficient to cause glaucoma. We found no statistical relationship between either anatomic success or functional result and the presence of aphakia, demarcation lines, vitreous hemorrhage, detachments of the pars plana epithelium, or predetachment glaucoma being treated.

In a retrospective study, 50 (8.2%) of 610 patients with malignant melanoma of the ciliary body or choroid had extrascleral extension. Of 46 patients for whom follow-up data were available, 24 (52%) survived five years, 20 (42%) survived ten years, and 17 (37%) survived 15 years. Factors that seemed to affect survival significantly included intraocular tumor size and extraocular tumor size and location. Our observations did not support the role of primary exenteration. Five patients (11%) with extrascleral extension had orbital recurrences and all died within 31 months of surgery regardless of treatment.

A 17-year-old boy had minor visual impairment, paracentral scotomata, and parafoveal retinal lesions following a presumed viral infection. Contact lens biomicroscopy demonstrated the retinal defects to be located at the level of the deep sensory retina. Fluorescein angiography revealed subtle areas of hypofluorescence which corresponded to the visible disturbances of the sensory retina. Follow-up examination three months later revealed persistent complaints of paracentral scotomata and persistent, but less recognizable retinal lesions. We believe the primary site of involvement to be the deep sensory retina.

In the elderly patient with a massive vitreous hemorrhage in one eye and senile macular choroidal degenerative changes in the fellow eye, a hemorrhagic disciform detachment causing this massive vitreous hemorrhage must be considered in the differential diagnosis. Ultrasonography selectively combined with radioactive phosphorus (32P) testing differentiates between a hemorrhagic disciform detachment or disciform scar and a malignant melanoma of the choroid. The ultrasonographic findings of a hemorrhagic disciform detachment may vary, but usually the posterior pole lesion is relatively flat and broad-based with a fairly homogeneous pattern without choroidal excavation. Posterior polar lesions secondary to senile macular choroidal degeneration do not grow. The vitreous hemorrhage clears in about three fourths of the patients, eventually allowing visualization of the posterior pole and ophthalmoscopic confirmation of a disciform scar. Almost one half of the eyes may be expected to lose all light perception because of the development of an initially hemorrhagic retinal detachment.

Four patients had malignant melanoma involving the conjunctiva, nasal cavity, and paranasal sinuses. In each patient, the conjunctival melanoma preceded recognition of the lesion in the nasal cavity by months or years. Each patient had one or more conjunctival biopsy specimens that documented melanoma, and in each patient the melanomas evolved in primary acquired melanosis of the conjunctiva. Histologic examination of the epithelium adjacent to the tumor in the nasal cavity failed to show either atypia or diffuse melanosis. We believe that these melanomas in the nasal cavity and paranasal sinuses are most likely to evolve as regional metastases, although it is possible that they arise de novo or as related foci in accordance with the multicentric characteristics of conjunctival melanoma. If a patient with a conjunctival melanoma has symptoms referable to the nasal cavity or paranasal sinuses, ophthalmologists should refer the patient to an otolaryngologist.

Among 173 patients who had rhegmatogenous retinal detachment with spared maculas, high percentage achieved anatomic and functional success. We reattached 171 (99%) of the retinas; 150 (76%) of the eyes had final visual acuities of 6/15 (20/50) or better. Eighteen eyes (10%) had final postoperative visual acuities reduced more than two lines from the preoperative level. This reduced visual acuity was primarily related to postoperative changes occurring in the macula. The prognosis both for anatomic reattachment and visual acuity after scleral buckling for rhegmatogenous retinal detachment is significantly better when the macula is spared than when it is not. Large numbers of cryoapplications were not associated with macular complications.

We reviewed our consultations and enucleations for suspected choroidal melanomas from 1954 through 1977. Among 876 eyes enucleated here during that period, 203 contained malignant melanomas; among these were 172 with melanomas of the choroid. Eighteen additional eyes contained melanomas of the anterior uvea. Six melanomas were clinically unsuspected. These unsuspected cases represented 2.6% of the 233 eyes in this series of enucleated eyes that were removed because of painful glaucoma, and 3.2% of the 190 uveal melanomas. Our study included eyes enucleated elsewhere after a clinical diagnosis of malignant melanoma was made here. Six of 224 eyes enucleated for clinically suspected melanoma were found to have mimicking lesions, a misdiagnosis rate of 2.7%. Two additional eyes were misdiagnosed as having simulating lesions before histologic confirmation of malignant melanoma after enucleation elsewhere.

Necrobiotic xanthogranuloma of the skin is associated with paraproteinemia and, often, with plasma proliferative disorders, including multiple myeloma. Other commonly recognized systemic abnormalities include hepatosplenomegaly, a highly increased erythrocyte sedimentation rate, and leukopenia. Fifteen of 16 patients (seven men and nine women with a mean age of 54 years) with this condition had ophthalmic manifestations. Thirteen patients had lesions affecting the skin of the eyelids and periorbital tissue; on casual examination these lesions resembled plane xanthoma. Unlike plane xanthoma, however, the lesions of necrobiotic xanthogranuloma were almost always indurated. Further, the lesions frequently became inflamed, leading to superficial ulceration. Deeper lesions occasionally involved the orbit. Yellow lesions were sometimes visible in the episcleral tissues where they were associated with recurrent symptoms of scleritis and episcleritis. Biopsy specimens of the skin lesions disclosed a distinctive pattern of subepidermal granulomatous masses with focal aggregates of histiocytes and giant cells surrounded by hyaline necrobiosis. Surgical excision of the eyelid lesions was often followed by recurrence and increased activity of the lesions. Low-dose chemotherapy is likely to produce a favorable response, with regard to both the skin lesions and the paraprotein abnormalities.

Confirmation of iodine-125 plaque position was determined with a modified fiberoptic light pipe that directed light at right angles to the long axis of the fiberoptic pipe. While the examiner observed the interior of the eye with indirect ophthalmoscopy, the point source of light from the fiberoptic light pipe was moved along the margins of the episcleral plaque. The position of the plaque relative to the location of the underlying melanoma could then be verified by transillumination.

We conducted a prospective study to determine the percentage of preoperative information that was retained by 100 patients undergoing a scleral buckling procedure. Each patient received a standardized preoperative discussion regarding the nature of retinal detachment and its management. During the immediate postoperative period, each patient was questioned about the informed consent discussion. Although 97% of the patients acknowledged a thorough preoperative discussion there was a definite disparity between the patients' concept of adequate physician disclosure and the actual retention of the preoperative explanation. Overall retention of preoperative disclosure based on correct answers to 12 questions was only 57%. Few patients, 23%, retained knowledge of surgical risks, and only 61% remembered that a foreign material would be permanently sutured to the eye. When a patient failed to remember the correct answer to a question, more than half of the time he or she denied that information relevant to the question had been discussed. The results of this study indicate that patients retain primarily information that seems to be in favor of their decision to have surgery.

Most iris tumors behave benignly, reflecting their small size and the high proportion of nevi and spindle A melanomas. Of 1,043 reported iris melanomas, 31 metastasized (3%). Metastasis from a spindle A melanoma is not known to occur despite documented growth and local recurrence after excision. If known spindle A melanomas are excluded from all reported spindle cell tumors of the iris, the rate of metastasis for spindle cell tumors is 2.6%. Mixed-cell melanomas have a metastasis rate of 10.5% and epithelioid melanomas a rate of 6.9%. The interval between the histologic diagnosis and death from metastases ranged from three months to 12 years, with an average of 6.5 years. Five- and ten-year mortality rates for different cell types cannot be ascertained. Iris angiography may be useful in defining the limits of tumor involvement but is of uncertain value in differentiating benignancy from malignancy. Of the 31 cases with metastases, 21 included information on the type of surgical procedure used to obtain the histologic diagnosis. In 13 of the 21 cases (62%), the tumors were initially involved with either incomplete excision or inadvertent transection before enucleation.

We analyzed data of 50 patients receiving long-term warfarin sodium therapy who underwent ocular surgery between 1982 and 1986. The frequency of hemorrhagic and thrombotic complications was compared in patients in whom anticoagulants were continued, those in whom the anticoagulants were discontinued in the perioperative period, and a group of matched control patients. There were six perioperative hemorrhagic complications in the warfarin-treated group (12%) compared to none in the control group. This difference was significant (P less than .03). However, no significant difference in hemorrhagic complications was seen between patients in whom warfarin sodium was continued and those in whom it was discontinued.

I designed this experiment to determine if spectacle lenses would protect against a No. 6 shot fired from a 12-gauge shotgun over progressively longer testing distances, and compared plastics, heat-tempered glass, and chemical-tempered glass lenses of standard and industrial thicknesses. The likelihood of a spectacle lens being hit by a well-centered shot pattern at 40, 50, and 60 yards was approximately 66%, 25%, and 20%, respectively. Virtually all lenses were destroyed at a testing distance of 30 yards. At 40 yards, standard-thickness plastic and heat-tempered lenses were destroyed but the chemical-tempered lenses offered some protection. At 40 yards, all types of industrial-thickness lenses provided protection but the most protection was provided by the chemical-tempered lenses. At 50 yards, chemical-tempered lenses offered more protection than either plastic or heat-tempered lenses. Throughout the experiment, plastic lenses performed no better than heat-tempered lenses.

We studied selective in vivo and in vitro immunologic factors of 25 patients with choroidal malignant melanoma. Immune profile factors did not show consistent differences between patients with melanoma and an age-matched control population. The studies were also non-contributory in delineating variations in immunocompetence with respect to melanoma cell types. Serial immune profiles failed to identify a change when clinical evidence of metastasis developed. When tested as a group, patients with melanoma in whom metastatic disease developed during the study showed significant depression of initial mitogen-induced lymphocyte blastogenesis. This depression was noted in advance of clinically recognized metastatic disease. This group had a wide range of responses that overlapped those of control patients, thus making the usefulness of these testing factors questionable for individual prognosis or for clinical monitoring.

We studied the incidence of rhegmatogenous retinal detachment in Rochester, Minnesota, for the nine-year period from 1970 through 1978. The age-adjusted rate for idiopathic rhegmatogenous retinal detachment was 10.1 per 100,000 population per year (45 cases). Including 12 cases of aphakic retinal detachments, the age-adjusted incidence was 12.9 per 100,000 population per year. Not surprisingly, the incidence rate increased with age in both sexes. By extrapolation from the Rochester rates, the number of cases per year of idiopathic retinal detachment in the United States would be expected to be about 22,000, and the number of both aphakic and idiopathic phakic cases per year would be expected to approach 28,000.

The role of argon laser photocoagulation in the management of central serous choriorectinopathy was evaluated in a prospective randomized study of eyes with leaks smaller than 250 microns in diameter in the early frames of the angiogram. Eyes were assigned to Group A when the leak was located in the papillomacular bundle or within 500 microns of the capillary-free zone and to Group B when the leakage site was located outside the papillomacular bundle and more than 500 microns from the capillary-free zone. Thirty eyes in Group A underwent either a sham argon laser treatment or a real argon laser treatment directed to the pigment epithelium under the elevated retina at a site remote from the site of fluorescein dye leakage (indirect laser photocoagulation). Twelve eyes in Group B underwent either a laser treatment directed to the site of fluorescein dye leakage (direct laser photocoagulation) or indirect laser photocoagulation. Compared with indirect photocoagulation, direct laser photocoagulation shortened the duration of central serous chorioretinopathy by approximately two months, a statistically significant difference. When compared to sham treatment, indirect photocoagulation did not significantly alter the duration of central serous chorioretinopathy. During an 18-month interval, the recurrence rate in the eyes treated with sham and indirect laser photocoagulation was 34%, whereas no recurrences were observed in the eyes treated with direct photocoagulation. There were no complications from photocoagulation in any of the eyes.

A 27-year-old male renal transplant recipient acquired cytomegalovirus (CMV) infection of both eyes. This was characterized early by a distinctive necrotic retinitis with discrete advancing edges. A large exudative retinal detachment and hypopyon developed in one eye, and cultures from the anterior chamber aspirate grew CMV. Cytomegalovirus was also isolated from the urine and throat; after serial negative base-line titers, CMV antibody titer became positive. At autopsy CMV was isolated from lung, esophagus, and kidney tissue. Light and electron microscopic studies demonstrated extensive necrosis and disruption of the sensory retina and retinal pigment epithelium with exudative retinal detachments. The diseased retinal cells contained a multiplicity of viral particles in various stages of maturity. Cytomegalic inclusion-bearing cells were demonstrated in the choroid of the more severely affected eye.

Eight cases of presumed small choroidal melanomas, associated with subretinal fluid in the macula, were studied to determine the eventual outcome of these tumors and the value of photocoagulation in eliminating subretinal fluid. Photocoagulation resulted in resolution of subretinal fluid involving the macula in six cases for a mean duration of 12 months. Six cases showed tumor growth over a mean interval of 24 months. Two cases were eventually managed with enucleation and two with I125 brachytherapy. The occurrence of subretinal fluid involving the macula in cases of small choroidal melanomas implies a high chance of subsequent tumor growth. Photocoagulation may be useful in eliminating subretinal fluid and improving vision during this observation period.

Continuous growth and an increase in pigmentation of a preretinal membrane occurred in a 46-year-old woman after a scleral buckling procedure for rhegmatogenous retinal detachment. Ten additional patients had pigmented preretinal membranes in eyes treated for rhegmatogenous retinal detachment. Although we made no attempts to determine the incidence of pigmented preretinal membrane formation in eyes with retinal detachments, these 11 cases, in a consecutive series of 500 eyes treated for rhegmatogenous retinal detachment, indicated that the development of pigmented preretinal membranes is not uncommon. Our clinical observations supported recent experimental findings implicating retinal pigment epithelial cells as a cause of preretinal membrane formation.

Multiple endocrine neoplasia type 2b is a syndrome, often familial, characterized by medullary carcinoma of the thyroid gland, pheochromocytoma, and many mucosal neuromas in patients who frequently have a marfanoid habitus. The ophthalmic findings are distinctive and include conjunctival and eyelid neuromas, keratoconjunctivitis sicca, and, most characteristically, greatly thickened corneal nerves. Ocular histopathologic study of a 30-year-old man demonstrated thickened nerves in the ciliary body, iris, and corneoscleral limbal regions. In these regions, the nerves were a mixture of myelinated and unmyelinated fibers. Sections through the thickened corneal nerves, 1.5 mm centrally from the corneoscleral limbus, showed only nonmyelinated nerves associated with Schwann cells. The many axons were normal in appearance but varied in diameter; some were between 0.1 and 0.2 ng and others between 1.0 and 1.4 ng. An unexpected finding was numerous ganglion cells in the ciliary body. The subconjunctival tissue showed neuromas with a minimum of fibrous structure. Sections of the lacrimal gland showed normal glandular tissue.

Ring scotomata were associated with fundus flavimaculatus in six patients. The demonstration of ring scotomata in patients with fundus flavimaculatus helps to explain persistent visual complaints that may exist in the presence of normal central visual acuity. In many instances, ring scotomata cannot be predicted on the basis of the ophthalmoscopic findings. The presence of ring scotomata appears to be an ominous finding, even when associated with normal central visual acuity, for in three of our patients it preceded loss of central vision by 1 1/2 to four years.

Uveal malignant melanomas were diagnosed in 15 patients in the resident population of Rochester and Olmsted County, Minnesota, from 1935 through 1974. There were five males and ten females. In this well-defined community, the annual incidence of uveal malignant melanoma for the 40-year period was calculated to be seven per million per year. The incidence in the resident population under age 50 years was three per million, whereas for those age 50 years or older, it increased to 21 per million per year.

Photic retinopathy was produced in two patients after a 60-minute exposure to light from an operating room microscope (Zeiss OpMi 6). The first patient had a blind eye with clear (phakic) media and a normal-appearing retina. A 60-minute exposure produced an oval gray lesion in the posterior pole at the level of the pigment epithelium. With an ultraviolet-400 filter added for a second exposure, a second lesion was produced. The second patient received a 60-minute exposure (without an ultraviolet filter) 72 hours before enucleation for a malignant melanoma. This produced photic retinopathy that resulted in a slight decrease in central visual acuity and a dense paracentral scotoma. This conclusively establishes a cause-and-effect relationship between exposure to the light from an operating room microscope and a retinal lesion in the human eye.

A 63-year-old man with a one-quadrant retinal detachment developed anterior segment ischemia after an operation that included the use of cryopexy, release of subretinal fluid, and segmental episcleral buckling without detachment of the extraocular muscles. A compromised cardiovascular condition of long duration and an episode of transient hypotension immediately preceding operation were factors in the pathogenesis of the ischemia. Although the anterior segment changes were moderately severe, recovery of vision ultimately was excellent.

In a review of patients with histologically verified malignant melanoma of the conjunctiva, we found 17 patients who had heavy pigmentation of the ipsilateral eyelid margin that was visible on external examination. Among nine patients in whom the histologic characteristics of the skin pigmentation could be studied, the features ranged from an increase in pigmentation of melanocytes within the basal layer to invasive malignant melanoma. The presence of heavy skin pigmentation in association with conjunctival melanoma appeared to be an ominous sign, even when the eyelid did not show histologic features of malignancy. Twelve of the 17 patients (70%) died of metastases after histologic verification of the conjunctival melanoma.

We did a long-term follow-up study of 42 patients aged 40 years and younger who had occlusion of the central retinal vein in order to learn its course and determine the frequency of related systemic disorders. Two groups of venous occlusion (complete and incomplete) were delineated by initial ocular findings. Final visual prognosis could not be predicted by the severity of the venous occlusion at the time of diagnosis. The presence of anomalous disk vessels closely correlated with a favorable prognosis in patients who had complete occlusion of the central retinal vein. None of the patients with incomplete central vein occlusion developed neovascular glucoma; three (14%) of the 21 patients with complete venous occlusion developed neovascular glucoma, which resulted in enucleation. Significant associated systemic maladies included cardiovascular disease and diabetes mellitus. An apparent correlation exists between occlusion of the central retinal vein and early death.

Delayed absorption of subretinal fluid beyond six weeks after surgical repair for rhegmatogenous retinal detachment was recognized in 39 of 575 consecutive cases of scleral buckling. The most common preoperative condition was large clumps of cells on the undersurface of the detached retina (subretinal precipitates). Approximately one in four patients in whom precipitates are seen preoperatively will have fluid persisting beyond six weeks from surgical repair to complete absorption. A second relatively common condition associated with delayed fluid absorption that could be recognized before operation was long-standing peripheral (usually inferior) retinal detachment, which typically spared the macula, was associated with demarcation lines, and was caused by round atrophic holes with or without associated lattice degeneration. An analysis of subretinal fluid protein concentrations in 39 cases showed a positive relationship between protein concentration and duration of detachment. Pigment-laden macrophages in the subretinal space, possibly originating from the retinal epithelium, were common.

In an experiment designed to simulate an excessively prolonged clinical examination, seven human eyes were exposed to light focused through a 20-diopter, aspheric condensing lens for 30 to 45 minutes. Three eyes contained primary malignant tumors of the choroid and were enucleated 1 1/2 to 4 1/2 days after light exposure. Follow-up data on four blind eyes with clear media were evaluated 15 to 36 months after light exposure. Concentrated prolonged light exposure used in this experiment caused grossly visible progressive corneal edema, along with significant discomfort to the patient. Even with light exposures sufficient to cause these complications of the anterior segment, retinal injury was recognizable only with electron microscopy and was characterized by irregular bending and twisting of the outer segments of the photoreceptors, changes that are considered reversible in nonhuman primate studies. Intermediate to long-term follow-up of 15 to 36 months after light exposure to blind eyes failed to reveal lens changes or delayed light-induced degenerative changes in the retina recognizable by ophthalmoscopy, fundus biomicroscopy, or color and fluorescein fundus photography.

In a study of the natural course and risk factors leading to visual impairment from retinal arterial macroaneurysms in 40 eyes (35 patients), we used a simple classification based on the anatomic location of the macroaneurysm and complicating factors. Group A included 17 eyes in which the exudate, edema, hemorrhage, or aneurysm (or a combination of these) was located within the vascular arcades and caused a decrease in central visual acuity. Group B included eight eyes in which the exudate, edema, hemorrhage, or aneurysm (or a combination of these) was located within the vascular arcades but did not cause a decrease in central visual acuity. Group C included 15 eyes in which the exudate, edema, hemorrhage, or aneurysm (or a combination of these) was located peripheral to the vascular arcades. Eyes in Group A with recent visual symptom had an uncertain prognosis and some were treated; eyes in Group B had a more favorable prognosis but required careful periodic examinations; and eyes in Group C had a favorable prognosis and almost always did well without treatment. Eyes with macroaneurysms hemorrhaging into the vitreous or under the inner limiting lamina also tended to recover.