Disorders of sex development: timing of diagnosis and management in a single large tertiary center.

BACKGROUND: We describe the phenotypic spectrum and timing of diagnosis and management in a large series of patients with disorders of sexual development (DSD) treated in a single pediatric tertiary center. METHODS: DSD patients who had visited our tertiary center during the survey period (between 2004 and 2014) were identified based on an ICD-10 inquiry, and their phenotypic and molecular genetic findings were recorded from patient charts. RESULTS: Among the 550 DSD patients, 53.3% had 46,XY DSD; 37.1% had sex chromosome DSD and 9.6% had 46,XX DSD. The most common diagnoses were Turner syndrome (19.8%, diagnosed at the mean age of 4.7 ± 5.5 years), Klinefelter syndrome (14.5%, 6.8 ± 6.2 years) and bilateral cryptorchidism (23.1%). Very few patients with 46,XY DSD (7%) or 46,XX DSD (21%) had molecular genetic diagnosis. The yearly rate of DSD diagnoses remained stable over the survey period. After the release of the Nordic consensus on the management of undescended testes, the age at surgery for bilateral cryptorchidism declined significantly (P < 0.001). CONCLUSIONS: Our results show that (i) Turner syndrome and Klinefelter syndrome, the most frequent single DSD diagnoses, are still diagnosed relatively late; (ii) a temporal shift was observed in the management of bilateral cryptorchidism, which may favorably influence patients' adulthood semen quality and (iii) next-generation sequencing methods are not fully employed in the diagnostics of DSD patients.

Transscleral red laser cyclophotocoagulation for the treatment of therapy-resistant inflammatory glaucoma.

PURPOSE: To evaluate in a retrospective study the long-term usefulness of red 647 nm krypton and 670 nm diode laser for transscleral contact cyclophotocoagulation (CPC) in the treatment of therapy-resistant inflammatory glaucoma. METHODS: The authors treated 48 eyes of 38 consecutive patients (mean age 36.8 years, range 6-81 years) with therapy-resistant inflammatory glaucoma secondary to chronic uveitis (45/48), chronic scleritis (1/48), or combined scleritis with keratouveitis (2/48) using transscleral red 647 nm Krypton or 670 nm Diode laser. All eyes had failed maximum tolerated medical therapy and 19/48 (40%) eyes also previous antiglaucoma surgery. Laser power at the scleral surface was 0.35 to 0.45 W and the application time 10 seconds each. The follow-up was 42.8+/- 40.0 (range 2-145) months. RESULTS: The mean preoperative intraocular pressure (IOP) of 35.6+/-8.1 mmHg fell to 6-21 mmHg level in 75% after one or repeated CPC. Among adult patients this was achieved in 85%, among children in 54%. More than one treatment was needed in 52%. No cases of hypotony, phthisis bulbi, or other devastating complications occurred. CONCLUSIONS: Transscleral CPC using red 647 nm krypton or 670 nm diode laser is an effective and well-tolerated procedure for the treatment of therapy-resistant inflammatory glaucoma in adults. CPC can be considered before incisional antiglaucoma surgery with a shunt or antimetabolites is undertaken.

Microvascular loops and networks as prognostic indicators in choroidal and ciliary body melanomas.

BACKGROUND: Malignant melanoma of the ciliary body and choroid of the eye is a tumor that disseminates frequently, and 50% of the diagnosed patients die within 10 years. We investigated the hypothesis that, by histopathologic analysis of the arrangement of microvessels (i.e., small blood vessels) in loops and networks, we might be able to differentiate better those patients with a favorable prognosis from those with a poor prognosis. METHODS: We conducted a population-based, retrospective cohort study of melanoma-specific and all-cause mortality for 167 consecutive patients who had an eye surgically removed because of malignant choroidal or ciliary body melanoma during the period from 1972 through 1981. Microvascular loops and networks were evaluated independently by two pathologists who were unaware of patient outcome. RESULTS: Microvascular patterns could be assessed in 134 (80%) of 167 melanoma specimens. The 10-year probability of melanoma-specific survival was worse if microvascular loops (0.45 versus 0.83; two-sided P<.0001) and networks (0.41 versus 0.72, two-sided P<.0001) were present. In multivariate Cox regression analysis of melanoma-specific survival, the hazard ratios were 1.66 (95% confidence interval [CI] = 1.19-2.30) for the presence of loops and networks as a combined three-category variable, 2.36 (95% CI = 1.37-4.05) for the presence of epithelioid cells, 1.11 (95% CI = 1.03-1.19) for the largest basal tumor diameter (evaluated as a continuous variable), and 2.14 (95% CI = 1.25-3.67) for ciliary body involvement. CONCLUSIONS: Patients with malignant uveal melanoma who have a favorable prognosis can be distinguished from those with a poor prognosis by histopathologic analysis of microvascular patterns in uveal melanoma tumor specimens.

Long-term maintenance of therapeutic response to lovastatin in patients with familial and non-familial hypercholesterolemia: a 3-year follow-up.

The 3-year efficacy of lovastatin alone or in combination with colestipol was evaluated in 54 patients with type 2 hyperlipoproteinemia (22 non-familial and 32 familial hypercholesterolemic patients). A sufficient and sustained reduction in LDL cholesterol was achieved in non-familial hypercholesterolemia with lovastatin alone (average dose 74 mg/day, range 40-80 mg/d), whereas combination therapy with lovastatin 80 mg/d and colestipol (average dose 11.9 g/d, range 5-20 g/d) was required in familial hypercholesterolemia. The percentage changes from baseline at 3 years in serum LDL cholesterol, HDL cholesterol and total triglycerides were in the lovastatin-only group -53%, +10% and -15%, respectively, and in the two-drug group -58%, +22% and -18%, respectively. A subgroup analysis in patients with non-familial hypercholesterolemia indicated that the lipid-modifying effects of lovastatin were similar in type 2A and 2B phenotypes, except for a greater triglyceride lowering effect in type 2B. The lovastatin-alone regimen was well tolerated, whereas addition of colestipol caused subjective side effects in many patients. Serious side effects or discontinuations due to therapies did not occur. Both therapies caused slight but significant increases (within normal limits) in average serum transaminase levels. After 36 months a significant rise of 1.7 kg in mean body weight was observed in the lovastatin-only group. The ophthalmological follow-up did not reveal any cataractogenic effect attributable to treatment during the 3.8-year follow-up period.

Cytoskeleton in neuroectodermally derived epithelial and muscle cells of the human iris and ciliary body.

The cytoskeleton of epithelial and muscle cells of the human iris and ciliary body was analyzed by immunohistochemistry in three morphologically normal formalin-fixed, paraffin-embedded eyes and in 34 eyes containing a uveal melanoma. Both layers of the iris epithelium reacted with monoclonal antibodies (MAb) V9 and Vim 3B4 to vimentin, whereas the ciliary epithelia additionally reacted with MAb CAM 5.2, CK5, KS-B17.2, and CY-90, recognizing cytokeratins 8 and 18. The same cytokeratin MAb labeled the retinal pigment epithelium, which lacked vimentin. The muscle portion of the anterior iris epithelium, which forms the dilator muscle, as well as the sphincter and ciliary muscles, reacted with MAb DE-U-10 to desmin and 1A4 to alpha-smooth muscle actin. The dilator and ciliary muscles also reacted with V9 and Vim 3B4 to vimentin, and some dilator fibers were weakly immunopositive for cytokeratin 8 and 18 with CY-90 and CAM 5.2. The antigenic profile of iris and ciliary epithelia infiltrated by melanoma cells remained unchanged. The intraocular epithelia, which are developmentally related but differ in function, and the intraocular muscles, which differ in origin but are functionally related, have distinct cytoskeletal profiles and may provide insights into the functional significance of intermediate filament expression.

Intermediate filaments in the human retina and retinoblastoma. An immunohistochemical study of vimentin, glial fibrillary acidic protein, and neurofilaments.

Fifty-five retinoblastoma specimens were studied by a sensitive immunoperoxidase method to determine the intermediate filament types present in human retina and retinoblastoma. Polyclonal antiserum against vimentin and monoclonal antibodies to glial fibrillary acidic protein (GFAP) and to the 200 kD neurofilament triplet protein were used. In the human retina, Müller's cells coexpressed vimentin and GFAP in most instances, probably as a reactive phenomenon. Surprisingly, the horizontal cells did not stain with any of the antibodies used, and may thus lack intermediate filaments. Also, the meshwork of neural fibers in the inner plexiform layer was unusually sparse. Retinoblastoma cells were found to be devoid of all intermediate filament types studied. The tumors contained, however, vimentin and GFAP in the stromal cells. All neurofilament-positive cells in retinoblastoma apparently derived from infiltrated retina. One retinoblastoma eye was also studied by indirect immunofluorescence microscopy of frozen sections with identical results.

Synaptophysin in the human retina and retinoblastoma. An immunohistochemical and Western blotting study.

Fifty-four formalin-fixed and paraffin-embedded intraocular retinoblastoma specimens and three human eyes enucleated because of orbital tumors were studied for the presence of synaptophysin, a neuron-associated integral membrane glycoprotein of presynaptic vesicles, by using the monoclonal antibody SY38. Normal human brain was used as control. In the human retina, synaptophysin-like immunoreactivity was present in both plexiform layers, but could not be detected in neuronal perikarya. However, in reactive retinas present in retinoblastoma eyes, synaptophysin was often observed in perikarya and processes of photoreceptors. Positive neoplastic cells were found in 45 of the 54 retinoblastomas. Differentiated tumors tended to contain greater numbers of positive cells than undifferentiated ones, a third of which were entirely negative. Identical immunoreactivity was seen in frozen specimens from human retina and from three retinoblastomas. Using Western blotting, a major polypeptide comigrating with human brain synaptophysin was detected in human retina, and a similar but slightly slower migrating band in retinoblastoma. The results support a primarily neuronal origin for this tumor and point to the possibility that synaptic elements, previously observed in a few cases, may be more frequent in retinoblastoma than had been thought.

Identification of a novel element in the human eye: the inner connective tissue layer of the ciliary body characterized with antibodies to the HNK-1 epitope.

PURPOSE: To characterize the nature and the developmental distribution of the HNK-1 epitope in the inner connective tissue layer of the human ciliary body, located between the ciliary epithelium and muscle with two monoclonal antibodies to the HNK-1 epitope common to many cell adhesion molecules. METHODS: Nine fetal (gestational age 13-40 wk) and 32 postnatal human eyes (age 3 mo to 78 yr) were studied by immunohistochemistry with monoclonal antibodies HNK-1 and VC1.1 to the HNK-1 epitope. Antibodies to cytoskeletal elements were used to characterize the cells in this region. RESULTS: The HNK-1-immunopositive cells appeared underneath the pigment epithelium of the pars plicata by the 20th gestational week, spread into the pars plana after the 28th week, and reached the ora serrata during the first year of life. The immunoreaction was constantly present in all adult eyes examined; they were sharply demarcated from the iris, ciliary muscle, and choroid. The HNK-1-positive subepithelial layer was not labeled with monoclonal antibodies V9 or Vim 3B4 to vimentin, monoclonal antibodies CAM 5.2 and CY-90 to cytokeratin 8 and 18, or monoclonal antibodies DE-U-10 and D33 to desmin in adult eyes, but was uniformly positive for vimentin in fetal eyes. The HNK-1 epitope was distributed along cell membranes or adjacent extracellular matrix of stromal cells. CONCLUSION: The HNK-1-positive stromal region is a constant and conspicuous element of the human eye that may have a role in structurally stabilizing the ciliary body, perhaps in relation to accommodation or aqueous secretion.

Cytoskeleton in normal and reactive human retinal pigment epithelial cells.

The cytoskeleton of normal and reactive retinal pigment epithelium (RPE) was analyzed immunohistochemically in five light microscopically normal formalin-fixed, paraffin-embedded human eyes enucleated because of orbital tumor and in 44 eyes with a uveal melanoma. In 26 eyes, the RPE overlying the tumor was morphologically normal or atrophic; in 18 eyes, hyperplastic changes were present. Normal RPE cells lacked vimentin, but it was present in 35 of 44 eyes with uveal melanoma. Antibodies that recognize cytokeratins CK8 and CK18 labeled normal and reactive RPE cells in all specimens. Although CAM 5.2 and CY-90 detected RPE cells strongly and quantitatively, clones CK5, KS-B17.2, and pancytokeratin antibody lu-5 reacted weakly and did not label some specimens. Immunoblotting supported the presence of CK8 and CK18 in human RPE. Normal RPE cells did not express other simple epithelial cytokeratins, but both atrophic and hyperplastic reactive RPE cells were labeled with antibodies to CK7 or CK19 in 24 of the 44 eyes. Hyperplastic proliferating RPE cells that formed subretinal membranes reacted positively for alpha-smooth muscle actin in 13 of 18 eyes. Antibodies to CK8 and CK18 are valuable markers of normal and reactive human RPE cells, but a panel of reagents is necessary to document reactive changes in the cytoskeleton. Acquisition of alpha-smooth muscle actin by human RPE cells may be related to their ability to form periretinal membranes and contribute to intraocular proliferative diseases.

Microvascular density in predicting survival of patients with choroidal and ciliary body melanoma.

PURPOSE: Although malignant uveal melanoma disseminates predominantly hematogenously because of the absence of intraocular lymphatics, consensus about prognostic impact of microvascular density (MVD) has not been reached. This study was undertaken to investigate whether MVD, microvascular patterns, or both determine prognosis of uveal melanoma. METHODS: A population-based retrospective cohort study of melanoma-specific and all-cause mortality of 167 consecutive patients who had an eye enucleated because of choroidal or ciliary body melanoma from 1972 through 1981 was conducted. MVD was determined by counting tumor vessels in a masked fashion from areas of highest vessel density after immunostaining for CD34 epitope, factor VIII-related antigen (FVIII-RAg), and alpha-smooth muscle actin (SMA). Kaplan-Meier and Cox regression analyses of survival were performed. The association between MVD and tumor size and location, cell type, and microvascular patterns was assessed. RESULTS: MVD could be determined from 134 of 167 melanomas (80%). Based on globally highest count obtained with antibodies to CD34, MVD ranged from 5 to 121 vessels/0.313 mm2 (median, 40) and its association with presence of microvascular loops and networks (P = 0.0006), epithelioid cells (P = 0.028), and largest basal tumor diameter (P = 0.0029) was statistically significant. The 10-year melanoma-specific mortality increased with MVD (0.09, 0.29, 0.59, and 0.64, according to quartiles; P < 0.0001), as did all-cause mortality (P = 0.0022). Equivalent results were obtained with immunostaining for FVIII-RAg, whereas MVD obtained with antibodies to SMA was not associated with prognosis. Cox regression showed a hazard ratio of 2.45 (95% CI, 1.43-4.18) for presence of epithelioid cells, 1.11 (95% CI, 1.03-1.20) for largest basal diameter, 1.23 (95% CI, 1.06-1.43) for square root-transformed MVD, and 1.51 (95% CI, 1.09-2.10) for presence of loops and networks, all of which independently contributed to prognosis. CONCLUSIONS: The findings support the theory that both MVD and microvascular patterns contribute independently to prognosis in uveal melanoma in addition to cell type and size of the tumor.

Immunohistochemical evidence for preproenkephalin A synthesis in human retinoblastoma.

Human retinoblastoma contains clusters of cells immunoreactive for methionine-enkephalin and methionine-enkephalin-arginine-phenylalanine. Some tumour cells also exhibited methionine-enkephalin-arginine-glycine-leucine-like immunoreactivity. The results are in agreement with those obtained with similar testing of neuroblastoma cell cultures. It is concluded that some human retinoblastoma cells are capable of synthesizing preproenkephalin A or parts of this molecule.

Tumor-infiltrating macrophages (CD68(+) cells) and prognosis in malignant uveal melanoma.

PURPOSE: To investigate the hypothesis that tumor-infiltrating macrophages contribute to prognosis of uveal melanoma and to study their association with tumor characteristics, especially microvessels. METHODS: This was a retrospective, population-based cohort study of 167 consecutive patients who had had an eye with choroidal and ciliary body melanoma removed between 1972 and 1981. Macrophages were identified with mAb PG-M1 to the CD68 epitope, and their number and morphologic type were recorded. Kaplan-Meier and Cox regression analyses of melanoma-specific survival were performed. RESULTS: CD68-positive macrophages could be assessed in 139 (83%) of the 167 melanomas. Their number was moderate to high in 115 (83%) of the 139 tumors, and their morphology ranged from dendritic to round. A high number of macrophages was associated with presence of epithelioid cells (P = 0.025), heavy pigmentation (P = 0.001), and high microvascular density (P = 0.001). The 10-year melanoma-specific mortality rate increased with higher numbers of macrophages (0.10 for low versus 0.57 for high numbers, P = 0.0012). The morphologic type of infiltrating macrophages was not associated with mortality. The number of macrophages was modeled by stratification, which significantly improved a Cox regression model (P < 0.001). Adjusting for the other independent indicators of metastatic death 10-year melanoma-specific mortality was 0.17 for low versus 0.45 for high numbers of macrophages. CONCLUSIONS: The number of tumor-infiltrating CD68-positive macrophages contributes to prognosis and associates with cell type and microvascular density, which merits a further analysis of the biological role of these cells in uveal melanoma.

Ocular amyloid deposition in familial amyloidosis, Finnish: an analysis of native and variant gelsolin in Meretoja's syndrome.

PURPOSE: To analyze the deposition of amyloid and its precursors in eyes of patients with familial amyloidosis, Finnish (FAF; Meretoja's syndrome), a hereditary systemic amyloidosis. METHODS: Autopsy eyes from three patients with FAF and ten control eyes were studied by Congo red staining and with antibodies to the nonmutated part of gelsolin (GS-2C4), the mutated gelsolin Asn-187 fragment (AGel), and amyloid-P component (AP). RESULTS: Congo red and antisera to AP and AGel bound to amyloid deposits in the cornea and conjunctiva, the sclera, the perineurium of ciliary nerves, the walls of ciliary vessels, the optic nerve sheaths, the stroma of the ciliary body, and along the choriocapillaris. mAb GS-2C4 bound weakly and focally to most deposits and strongly around the choriocapillaris. It labeled the corneal epithelium and endothelium, keratocytes, scleral fibroblasts, trabecular and lens epithelial cells, the ciliary muscle and epithelium, the iris sphincter and dilator, and stromal cells of the conjunctiva and uveal tract. CONCLUSIONS: Local production, especially in the cornea, conjunctiva, sclera, and ciliary muscle, and systemic deposition, particularly in blood vessles and in the sclera, may contribute to amyloid deposits in FAF. To explain the complex pattern of deposition, microenvironmental factors such as lamellar architecture of the cornea and sclera, altered processing of gelsolin, or blood-tissue barriers must be invoked. In addition to corneal lattice dystrophy type II, the observed deposits help to explain glaucoma in patients with FAF.

Tear fluid plasmin activity after excimer laser photorefractive keratectomy.

PURPOSE: Elevated tear fluid plasmin activity may correlate with delayed healing of corneal wounds. The present study was performed to establish the tear fluid plasmin activity after photorefractive keratoablation (PRK). METHODS: Tear fluid aspirated with microcapillaries was subjected to a fluorometric plasmin assay using the 7-amido-4-trifluoromethylcoumarin derivate of the tripeptide H-D-Val-Leu-Lys as substrate. RESULTS: Tear fluid flow, plasmin activity, and flow-corrected plasmin excretion rate in tears (plasmin flux) were determined preoperatively and 1, 2, and 7 days after PRK. The preoperative tear fluid flow was 6.55 microliters/min (median; range, 1.8 to 21.8 microliters/min), plasmin activity was 1.29 IU/l (median; range, 0.6 to 6.9 IU/l), and the excretion of plasmin in tears was 11.7 microIU/min (median; range, 1.6 to 41.5 microIU). A statistically significant decrease in tear fluid plasmin activity was found during the follow-up period on the first (0.6 IU/l; range, 0.6 to 1.7 IU/l, P < 0.01) and second (0.65 IU/l; range, 0.6 to 1.49 IU/l, P < 0.01) postoperative days. On the other hand, significant elevation of both tear fluid flow and plasmin flux values occurred during the first two postoperative days. The median plasmin flux values on days 1, 2, and 7 were 57.35 microIU/min (range, 16 to 540 microIU/min, P < 0.01), 40.0 microIU/min (range, 13.3 to 222.8 microIU/min, P < 0.01), and 10.2 microIU/min (range, 2.2 to 90.7 microIU/min, P > 0.05), respectively. CONCLUSION: The marked elevation of tear fluid flow coincided with the persistence of an epithelial defect. However, because of the acceleration of tear fluid flow, proteolytic activity due to plasmin (IU/l) actually decreases. Consequently, the increased excretion of plasmin in tears (plasmin flux) does not lead to highly elevated plasmin activity, which could inhibit wound healing. It seems to be a natural healing response because all corneas were epithelialized normally by or on day 3.

Expression of tenascin and cellular fibronectin in the rabbit cornea after anterior keratectomy. Immunohistochemical study of wound healing dynamics.

Anterior keratectomy (AKE) was done on rabbits, and the appearance of immunohistochemically demonstrable tenascin (TN) or cellular fibronectin (cFN) was studied at different times (5 min to 14 months) after the operation. The substance TN was first observed 12 hr after wounding in the posterior stroma; cFN appeared with the same localization 12 hr later. During postoperative week 1, both TN and cFN immunoreactions shifted to more anterior parts of the cornea, and 9 days after wounding, they were localized in the most anterior part of the stroma only. Thereafter the reactions gradually decreased in intensity but still were visible 3 months after AKE. No reaction for TN or cFN was present 14 months postoperatively.

Primitive neuroectodermal tumor of the midbrain in a murine model of retinoblastoma.

The first heritable model of retinoblastoma was established by retina-specific expression of simian virus 40 T-antigen (SV40 T-ag) in transgenic mice. Bilateral, multifocal ocular tumors were observed in 100% of transgene-bearing mice. Central nervous system neoplasms occurred at a lower rate (27%) and represented the murine counterpart of human trilateral retinoblastoma. The authors characterized the transgenic brain tumors and found them to be primitive neuroectodermal tumors (PNET) of the midbrain. Murine brain tumors do not involve the pineal gland and most closely resemble undifferentiated suprasellar or parasellar tumors occasionally observed in human trilateral retinoblastoma. The murine malignancies arose from the subependymal cells of the cerebral aqueduct. Immunohistochemical and ultrastructural examination revealed that the transgenic brain tumors were undifferentiated and lacked all antigens associated with normal murine neuronal, glial, and ependymal cells.

Corneal morphology and sensitivity in lattice dystrophy type II (familial amyloidosis, Finnish type).

PURPOSE: To describe the corneal abnormalities and to measure different modalities of corneal sensitivity in corneal lattice dystrophy type II (familial amyloidosis, Finnish type, also known as gelsolin-related amyloidosis and originally as Meretoja syndrome). METHODS: Twenty eyes of 20 patients were examined by in vivo confocal microscopy and noncontact gas esthesiometry. RESULTS: Pleomorphism of, and dense deposits between or posterior to, the basal epithelial cells were frequently observed, as well as a reduction of long nerve fiber bundles in the subbasal nerve plexus. The anterior stroma was altered in most cases, with fibrosis and abnormal extracellular matrix. In 15 corneas, thick anterior and midstromal filaments, corresponding to lattice lines, and in 11 corneas, thin undulated structures were observed. The average mechanical sensitivity threshold of 12 subjects was increased, and in the remaining 8 subjects there was no response, even to the highest intensity of stimuli used. Three patients did not respond to CO(2), 11 to heat, and 2 to cold, but those patients who responded had normal thresholds. Patients with more long nerve fiber bundles per confocal microscopic image had better mechanical and cold sensitivity than patients with fewer nerve fiber bundles. CONCLUSIONS: Lattice lines seem to be related to amyloid material and not to corneal nerves. However, the subbasal nerve density appears reduced, which results mainly in a decrease in mechanical and, to a lesser extent, thermal sensitivity. The location of stromal filaments and undulated structures changes with increasing age.

Immunoreactivity of exfoliation material for the cell adhesion-related HNK-1 carbohydrate epitope.

OBJECTIVE: To study the presence of the HNK-1 epitope in exfoliation material. METHODS: Twenty-six formalin-fixed, paraffin-embedded human eyes with exfoliation syndrome and 30 control eyes were studied immunohistochemically with monoclonal antibodies HNK-1 and VC1.1 to the HNK-1 epitope. RESULTS: Exfoliation material reacted consistently with antibodies to the HNK-1 epitope. The zonular lamella of the lens, inner surface of the nonpigmented ciliary epithelium, and inner connective tissue layer of the ciliary body were also labeled, but the lens capsule, epithelium, and zonules were not immunoreactive. Several blood vessels of the iris showed granular immunoreaction beneath the endothelium in all exfoliation eyes and in 11 (37%) of 30 control eyes, representing older age groups. CONCLUSIONS: The zonular lamella, nonpigmented ciliary epithelium, or the inner connective tissue layer may be responsible for the HNK-1 epitope in exfoliation material. Since this epitope is shared by many cell-adhesion molecules, its presence in exfoliation material might be of pathogenetic significance to the formation of the deposits.

Management of traumatic hyphema in children. An analysis of 340 cases.

Three hundred forty children with nonperforating traumatic hyphema were examined to verify or refute the possible protective action of the antifibrinolytic agent, tranexamic acid, against rebleeding. In the retrospective study group, 219 children were treated with strict bed rest, binocular patching, and sedation but did not receive antifibrinolytic agents. In the prospective study group, 121 children received systemically administered tranexamic acid; some of these children were confined to bed rest (26 cases) and some were allowed free ambulation within their rooms (95 cases). In the children who were treated with bed rest but who did not receive the antifibrinolytic agent, the frequency of secondary hemorrhage was 9.6%. Tranexamic acid reduced the incidence of secondary hemorrhage significantly: none of 26 eyes of patients who received systemically administered tranexamic acid and were confined to bed rest rebled, and only one (1.1%) of 95 eyes of children who received tranexamic acid and were allowed free ambulation in the hospital rebled.

Clinically successful contact transscleral krypton laser cyclophotocoagulation. Long-term histopathologic and immunohistochemical autopsy findings.

OBJECTIVE: To report long-term histopathologic findings 10 months after contact transscleral krypton cyclophotocoagulation. METHODS: The tissue response in a successfully treated eye was analyzed by light microscopy and a panel of 11 antibodies to epithelial, mesenchymal, and inflammatory cells. RESULTS: A 75-year-old man with uncontrolled angle recession glaucoma was treated with transscleral contact krypton cyclophotocoagulation (17 burns, 3.5 J each) 10 months before his death. The intraocular pressure fell from 28 to 17 mm Hg 6 months after therapy. Confluent scars straddled the posterior pars plicata and the anterior pars plana. The ciliary processes were destroyed, but the sclera and zonules were intact. Vimentin and cytokeratin 8 and 18 persisted in the degenerated ciliary epithelium. The inner connective-tissue layer and the ciliary muscle had atrophied, as shown with antibodies to the HNK-1 epitope, desmin, and alpha-smooth-muscle actin. Macrophages with phagocytized pigment and single T cells were present instead. No unusual inflammatory infiltrate was present in the choroid of either eye. CONCLUSIONS: Clinically effective ablation of ciliary processes is achieved with contact krypton laser. Little chronic inflammation and no signs of sympathetic ophthalmia were present. Atrophy of the ciliary muscle may reduce accommodative capacity in younger patients undergoing cyclophotocoagulation.