PURPOSE: Immunohistochemical studies have begun to advance knowledge regarding the pathogenesis of vascular anomalies in many anatomical regions. However, the immunohistochemical features of most orbital tumors have been overlooked. Therefore, a comparative immunohistochemical study of a series of the 2 most common orbital vascular lesions- infantile hemangioma (IH) and encapsulated cavernous venous lesion (ECVL), the latter also termed cavernous hemangioma or venous malformation-was undertaken. METHODS: Twenty surgically excised orbital tumors diagnosed clinically and histopathologically as IHs (10 cases) or "cavernous hemangioma" (10 cases) were evaluated pathologically and immunohistochemically using hematoxylin and eosin, Alcian blue, Masson trichrome, GLUT-1, CD31, CD34, D2-40, smooth muscle actin (SMA), desmin, and Ki-67 probes. RESULTS: All cases reacted strongly with the traditional blood vessel endothelial markers CD31 and CD34 and were negative for D2-40, a selective marker for lymphatic endothelium. All IH were positive for GLUT-1, and all ECVL were negative for GLUT-1. In IH, SMA (but not desmin) stained a monolayer of pericytes and in ECVL multilaminar smooth muscle vascular mural cells and intravascular (interstitial) stromal cells. Nuclear Ki-67 immunostaining was strongly positive in IH (average of 16.3%) and close to zero in ECVL. CONCLUSIONS: Immunophenotypic results for ECVL and IH demonstrated no overlapping staining patterns. Infantile hemangioma had the classical architecture of capillaries. Because of the constant presence of mural smooth muscle, it was concluded that ECVL is an accurate and descriptive term. However, desmin negativity in ECVL indicates myofibroblastic differentiation rather than full-fledged smooth muscle differentiation. Infantile hemangioma may display ectatic channels as the lesion ages but does not acquire multilaminar smooth muscle walls. Its pericytes lack cytoplasmic filaments and desmin reactivity but are SMA-positive because of the presence of poorly polymerized actin in the cytosol. In IH, Ki-67 positivity was observed in the endothelial cells of the solid and more ectatic regions. In contrast, the virtual absence of Ki-67 positivity in ECVL lends further support for the interpretation that it is more closely related to a malformation than a benign neoplasm.

PURPOSE: Infants with orbital hemangiomas and vascular malformations often develop expanded orbits or regional hyperostosis. Treatment in these cases depends, in part, on the stage of orbital development at the time of intervention; yet, orbital development with respect to age is not well-known. The authors sought to determine the rate of orbital development and the age of orbital maturation in a single ethnic population. METHODS: Skeletons recovered in North America and housed at the Peabody Museum of Archaeology and Ethnology, Harvard University, were inspected. The age of specimen was determined by dentition. Orbital volume was measured using 1-mm glass beads and a graduated cylinder. Linear measurements were taken with calipers and paper rulers. The measurements were plotted against age, and statistical analysis was performed. Relevant literature was reviewed. RESULTS: Of the hundreds of skeletons examined, 42 were sufficiently intact for orbital measurement. The specimens represented a period of up to 1000 years. Thirty-two were pediatric (defined prenatal to 18 years) and 10 were adults. Mean adult orbital volume was 26.2 ml. Based on the regression analysis, 60% of adult orbital volume was achieved at 4.35 years, 75% at 9.36 years, and 90% at 17.13 years of age. Linear dimensions progressively increased with age. CONCLUSIONS: This largest direct-measure study of pediatric orbital volume suggests that orbital growth continually decelerates from birth until maturity at 22 years. With 50% of orbital growth occurring by 16 months of age, surgeons removing periocular vascular anomalies after that age should consider concurrent skeletal management.

PURPOSE: To report a case of corneal hydrops in a patient with keratoglobus that was managed with endothelial keratoplasty to achieve corneal stability and prevent a limbus-to-limbus tear in Descemet membrane. METHODS: A 30-year-old man with keratoglobus presented with corneal hydrops in his left eye resulting from a central vertical tear in Descemet membrane. His other eye had been previously treated with penetrating keratoplasty using a large graft (an 11-mm donor graft to a 10-mm recipient bed) because of a limbus-to-limbus tear in Descemet membrane without resolution of his edema. An attempt to approximate the edges of the Descemet tear in the left eye by an intracameral air injection failed, and the tear continued to progress peripherally. An endothelial keratoplasty button with anchoring sutures was placed over the Descemet tear because of excessive localized edema. RESULTS: One month after insertion of the sutured endothelial keratoplasty button, the edema had resolved, and 1 year later, the tear remains sealed. The patient's visual acuity improved from counting fingers at 1 foot to 20/100. CONCLUSIONS: Reconstitution of the posterior corneal surface in keratoglobus-induced hydrops can be achieved with endothelial keratoplasty over the Descemet tear. Preventing progression of a central Descemet tear is essential to bypass the need for a large-diameter penetrating keratoplasty graft and its complications in a young patient with a history of bilateral corneal hydrops.

PURPOSE: To evaluate the use of the Boston keratoprosthesis type I implantation in patients with mucous membrane pemphigoid (MMP). METHODS: Retrospective review of 8 eyes of 8 patients with severe ocular surface disease and corneal blindness as a result of MMP who underwent Boston keratoprosthesis type I implantation at the Massachusetts Eye and Ear Infirmary from January 1, 2000, through December 31, 2009. The main outcome measures were best-corrected visual acuity, keratoprosthesis retention, and postoperative complications. RESULTS: The mean age of patients was 71.3 years (range, 55-94 years), and the mean duration of their disease preoperatively was 6.1 years (range, 1.7-11.4 years). Visual acuity after the surgery improved to 20/200 or better in 6 eyes (75%) and to 20/40 or better in 3 eyes (37.5%). Only 1 of 6 eyes (16.7%) was able to maintain visual acuity of 20/200 or better over a mean follow-up period of 3.2 years. Five of the 8 Boston keratoprosthesis type I devices (62.5%) extruded or had to be replaced during a mean follow-up time of 1.7 ± 1.7 years. Loss of vision to worse than 20/200 during the follow-up period occurred because of keratoprosthesis type I extrusion, end-stage glaucoma, and retinal or choroidal detachment. CONCLUSIONS: The clinical outcomes of Boston keratoprosthesis type I implantation in MMP are guarded and, as judged from the literature, less favorable than those with the Boston keratoprosthesis type II for the same disease.

PURPOSE: To present a case with bilateral choroidal neovascularization (CNV) secondary to acute disseminated encephalomyelitis-associated choroiditis requiring immunomodulatory therapy for prevention of recurrence. METHODS: The clinical course of a patient diagnosed with acute disseminated encephalomyelitis, who developed bilateral choroiditis at the time of his neurologic diagnosis and bilateral CNV 6 years later, is reviewed. PATIENT: A 57-year-old man developed CNV in both eyes, 6 years after the initial diagnosis of acute disseminated encephalomyelitis-associated choroiditis. The patient was initially treated successfully with intravitreal bevacizumab injections and oral prednisone, but CNV recurred with steroid tapering. Mycophenolate mofetil was initiated as steroid-sparing immunomodulatory therapy. RESULTS: There was no CNV recurrence for 1.5 years without the need for additional antiangiogenic therapy. CONCLUSION: To our best knowledge, this is the first report of choroiditis and secondary CNV associated with acute disseminated encephalomyelitis. In cases of recurrent CNV associated with choroiditis, systemic therapy should be strongly considered in conjunction with antiangiogenic therapy. The recurrence of CNV with tapering of oral steroids and the remission of CNV with steroid-sparing immunomodulatory therapy support the role of ongoing inflammation in the pathogenesis.

A 44-year-old man with neurofibromatosis type 1 had been aware that his right eye pulsated. His visual acuity was 20/15 in both eyes and his intraocular pressures were normal. He had 4 mm of right exophthalmos and there was pulse-synchronous pulsation of the right eye (video on the Neurology® Web site at www.neurology.org). No bruit was heard. Lisch nodules were present on both irides. CT showed a large osseous defect of the greater wing of the right sphenoid bone. The differential diagnosis of pulsatile proptosis includes absence of the sphenoid wing in patients with neurofibromatosis 1,(1) carotid-cavernous fistula, orbital roof fractures, and arteriovenous malformations.(2.)

PURPOSE: To determine whether the blue arc entoptic phenomenon, a positive visual response originating from the retina with a shape that conforms to the topology of the nerve fiber layer, is depressed in glaucoma. METHODS: We recruited a cross-sectional, nonconsecutive sample of 202 patients from a single institution in a prospective manner. Subjects underwent full ophthalmic examination, including standard automated perimetry (Humphrey Visual Field 24-2) or frequency doubling technology (Screening C 20-5) perimetry. Eligible patients viewed computer-generated stimuli under conditions chosen to optimize perception of the blue arcs. Unmasked testers instructed patients to report whether they were able to perceive blue arcs but did not reveal what response was expected. We created multivariable logistic regression models to ascertain the demographic and clinical parameters associated with perceiving the blue arcs. RESULTS: In multivariable analyses, each 0.1 unit increase in cup-disc ratio was associated with 36% reduced likelihood of perceiving the blue arcs (odds ratio [OR] = 0.66 [95% confidence interval (CI): 0.53-0.83], P<.001). A smaller mean defect was associated with an increased likelihood of perceiving the blue arcs (OR=1.79 [95% CI: 1.40-2.28]); P<.001), while larger pattern standard deviation (OR=0.72 [95% CI: 0.57-0.91]; P=.005) and abnormal glaucoma hemifield test (OR=0.25 [0.10-0.65]; P=.006) were associated with a reduced likelihood of perceiving them. Older age and media opacity were also associated with an inability to perceive the blue arcs. CONCLUSION: In this study, the inability to perceive the blue arcs correlated with structural and functional features associated with glaucoma, although older age and media opacity were also predictors of this entoptic response.

PURPOSE: To assess the association between single nucleotide polymorphisms (SNPs) of the gene region containing cyclin-dependent kinase inhibitor 2B antisense noncoding RNA (CDKN2B-AS1) and glaucoma features among primary open-angle glaucoma (POAG) patients. DESIGN: Retrospective observational case series. METHODS: We studied associations between 10 CDKN2B-AS1 SNPs and glaucoma features among 976 POAG cases from the Glaucoma Genes and Environment (GLAUGEN) study and 1971 cases from the National Eye Institute Glaucoma Human Genetics Collaboration (NEIGHBOR) consortium. For each patient, we chose the feature from the eye with the higher value. We created cohort-specific multivariable models for glaucoma features and then meta-analyzed the results. RESULTS: For 9 of the 10 protective CDKN2B-AS1 SNPs with minor alleles associated with reduced disease risk (eg, the G allele at rs2157719), POAG patients carrying these minor alleles had smaller cup-to-disc ratio (0.05 units smaller per G allele at diagnosis; 95% CI: -0.08, -0.03; P = 6.23E-05) despite having higher intraocular pressure (IOP) (0.70 mm Hg higher per G allele at DNA collection; 95% CI: 0.40, 1.00; P = 5.45E-06). For the 1 adverse rs3217992 SNP with minor allele A associated with increased disease risk, POAG patients with A alleles had larger cup-to-disc ratio (0.05 units larger per A allele at diagnosis; 95% CI: 0.02, 0.07; P = 4.74E-04) despite having lower IOP (-0.57 mm Hg per A allele at DNA collection; 95% CI: -0.84, -0.29; P = 6.55E-05). CONCLUSION: Alleles of CDKN2B-AS1 SNPs, which influence risk of developing POAG, also modulate optic nerve degeneration among POAG patients, underscoring the role of CDKN2B-AS1 in POAG.

PURPOSE: Circulating estrogen levels are relevant in glaucoma phenotypic traits. We assessed the association between an estrogen metabolism single nucleotide polymorphism (SNP) panel in relation to primary open angle glaucoma (POAG), accounting for gender. METHODS: We included 3,108 POAG cases and 3,430 controls of both genders from the Glaucoma Genes and Environment (GLAUGEN) study and the National Eye Institute Glaucoma Human Genetics Collaboration (NEIGHBOR) consortium genotyped on the Illumina 660W-Quad platform. We assessed the relation between the SNP panels representative of estrogen metabolism and POAG using pathway- and gene-based approaches with the Pathway Analysis by Randomization Incorporating Structure (PARIS) software. PARIS executes a permutation algorithm to assess statistical significance relative to the pathways and genes of comparable genetic architecture. These analyses were performed using the meta-analyzed results from the GLAUGEN and NEIGHBOR data sets. We evaluated POAG overall as well as two subtypes of POAG defined as intraocular pressure (IOP) ≥22 mmHg (high-pressure glaucoma [HPG]) or IOP <22 mmHg (normal pressure glaucoma [NPG]) at diagnosis. We conducted these analyses for each gender separately and then jointly in men and women. RESULTS: Among women, the estrogen SNP pathway was associated with POAG overall (permuted p=0.006) and HPG (permuted p<0.001) but not NPG (permuted p=0.09). Interestingly, there was no relation between the estrogen SNP pathway and POAG when men were considered alone (permuted p>0.99). Among women, gene-based analyses revealed that the catechol-O-methyltransferase gene showed strong associations with HTG (permuted gene p≤0.001) and NPG (permuted gene p=0.01). CONCLUSIONS: The estrogen SNP pathway was associated with POAG among women.