Buphthalmic Eye Research Articles

“Coming up short” with an illuminated microcatheter for circumferential trabeculotomy ab externo in the buphthalmic infant eye: frequency and options

Angle surgery constitutes initial surgical treatment for most primary congenital glaucoma (PCG) cases. An illuminated microcatheter (iTrack microcatheter/Nova Eye Medical, Fremont, CA) facilitates circumferential trabeculotomy (360trab) but may not “reach” 360° in buphthalmic PCG eyes. This study’s purpose is the creation and validation of a model using preoperative horizontal corneal diameter (HCD) to predict whether the iTrack will traverse all 360° of Schlemm canal (SC) to assist surgical planning.

Childhood Glaucoma

Childhood glaucoma is a rare disease. Since a lacking therapy normally leads to blindness an immediate diagnosis and appropriate treatment are crucial. The heterogeneity of childhood glaucoma requires a comprehensive knowledge of possible underlying pathomechanisms of primary and secondary childhood glaucoma types. Several types of childhood glaucoma are accompanied with ocular or systemic syndromes and hereditary causes are frequent. Thus, an interdisciplinary team of ophthalmologists, orthoptists, pediatricians, human geneticists, and anesthesiologists is vital for a successful supply. Most cases rely on a dysgenesis of trabecular meshwork with impaired outflow. Thus, usually a surgical approach is indicated. To handle a surgery in a buphthalmic eye an experienced hand is required. Special attention should be paid on the correct prescription of topical antiglaucomatous therapy in children since they are more prone to develop side effects. This article aims to provide an overview about the different childhood glaucoma types and to point out the most important aspects of their individual treatment strategies.

Dysfunction of the limbal epithelial stem cell niche in aniridia-associated keratopathy

PurposeAbnormalities in the limbal niche microenvironment have been suggested to be causally involved in aniridia-associated keratopathy (AAK), but histological analyses on the limbal structure and composition in AAK are lacking. Here, we investigated morphologic and molecular alterations of the limbal epithelial stem cell niche in human congenital aniridia. MethodsThe blind, buphthalmic and painful left eye of a 16-year old girl with congenital aniridia and juvenile glaucoma had to be enucleated because of uncontrolled intraocular pressure. The diagnosis of AAK was based on classical clinical features and partial limbal stem cell deficiency in the superior half. Genetic analysis identified a large heterozygous PAX6 gene deletion encompassing exons 11–15 as well as exon 9 of the neighboring ELP4 gene. Three limbal biopsies were taken from the superior, nasal and temporal regions to isolate and cultivate limbal epithelial progenitor cells and subject them to mRNA expression analyses. The globe was vertically bisected and processed for light and transmission electron microscopy and immunohistochemistry. ResultsComparative analysis of the superior and inferior limbal zones showed a gradual degradation of palisade structures associated with the transition from a hyperplastic to an attenuated corneal epithelium, inflammatory cell infiltrations and basement membrane irregularities. The clinically unaffected inferior part revealed no distinct stem cell clusters in the preserved palisade region, but a uniform population of hyperproliferative, undifferentiated progenitor cells in the basal/suprabasal layers of limbal and corneal epithelia, which gave rise to maldifferentiated epithelial cells exhibiting a conjunctival/epidermal phenotype and nuclear-to-cytoplasmic translocation of Pax6. The structure of the limbal niche was fundamentally perturbed, showing marked alterations in extracellular matrix composition, dislocation of atypical melanocytes lacking melanosomes and melanin, aberrant Wnt/β-catenin and retinoic acid signaling, and massive immune cell infiltration. ConclusionsConsidering the limitations of a single Case study, the findings suggest that ocular surface alterations in AAK are caused by a primary dysfunction and gradual breakdown of the limbal stem cell niche through Pax6-related effects on both melanogenesis and epithelial differentiation.

Imaging Distal Aqueous Outflow Pathways in a Spontaneous Model of Congenital Glaucoma.

PurposeTo validate the use of aqueous angiography (AA) in characterizing distal aqueous outflow pathways in normal and glaucomatous cats.MethodsEx vivo AA and optical coherence tomography (OCT) were performed in nine adult cat eyes (5 feline congenital glaucoma [FCG] and 4 normal), following intracameral infusion of 2.5% fluorescein and/or 0.4% indocyanine green (ICG) at physiologic intraocular pressure (IOP). Scleral OCT line scans were acquired in areas of high- and low-angiographic signal. Tissues dissected in regions of high- and low-AA signal, were sectioned and hematoxylin and eosin (H&E)-stained or immunolabeled (IF) for vascular endothelial and perivascular cell markers. Outflow vessel numbers and locations were compared between groups by Student's t-test.ResultsAA yielded circumferential, high-quality images of distal aqueous outflow pathways in normal and FCG eyes. No AA signal or scleral lumens were appreciated in one buphthalmic FCG eye, though collapsed vascular profiles were identified on IF. The remaining eight of nine eyes all showed segmental AA signal, distinguished by differences in time of signal onset. AA signal always corresponded with lumens seen on OCT. Numbers of intrascleral vessels were not significantly different between groups, but scleral vessels were significantly more posteriorly located relative to the limbus in FCG.ConclusionsA capacity for distal aqueous humor outflow was confirmed by AA in FCG eyes ex vivo but with significant posterior displacement of intrascleral vessels relative to the limbus in FCG compared with normal eyes.Translational RelevanceThis report provides histopathologic correlates of advanced diagnostic imaging findings in a spontaneous model of congenital glaucoma.

Precise Short Sequence Insertion in Zebrafish Using a CRISPR/Cas9 Approach to Generate a Constitutively Soluble Lrp2 Protein.

LRP2 is a large transmembrane receptor expressed on absorptive epithelia where it binds many extracellular ligands to control several signaling pathways. Mutations in LRP2 are associated with buphthalmic eye enlargement, myopia and other non-ocular symptoms. Though studies have clearly shown that absence of LRP2 causes these phenotypes, and that overexpression of individual LRP2 domains can exacerbate eye enlargement caused by the absence of Lrp2, the relationship between soluble LRP2 fragments and full-length membrane-bound LRP2 is not completely understood. Here we use a CRISPR/Cas9 approach to insert a stop codon cassette into zebrafish lrp2 to prematurely truncate the protein before its transmembrane domain while leaving the entire extracellular domain intact. The resulting mutant line will be a useful tool for examining Lrp2 function in the eye, and testing hypotheses regarding its extracellular processing.

Clinical Outcome of Rebubbling for Graft Detachment After Descemet Membrane Endothelial Keratoplasty.

To assess the clinical outcome after successful rebubbling procedures for visually significant graft detachment after Descemet membrane endothelial keratoplasty (DMEK). From a total of 760 consecutive DMEK surgeries, 41 eyes required rebubbling. Of those, 33 eyes of 31 patients were successful and were included in our retrospective outcome analysis study. Main outcome measures were compared with those of matched controls with uneventful primary DMEK (attached DMEK grafts without rebubbling). Rebubbling was performed on average 25 (±20) days (range 7-91 days) after DMEK. All eyes were evaluated for best-corrected visual acuity, endothelial cell density (ECD), pachymetry, and complications up to 6 months after rebubbling. At 6 months after DMEK, best-corrected visual acuity in rebubbled eyes did not differ from that in control eyes (P = 0.514). The mean ECD decrease was higher in rebubbled than in control eyes (54% vs. 35%, respectively, P = 0.001). Pachymetry did not differ between both groups (P = 0.153). After rebubbling, one buphthalmic eye showed temporary intraocular pressure elevation and 5 eyes had minor graft edge detachment that did not require further treatment. Rebubbling for DMEK graft detachment may result in similar visual outcomes as in uncomplicated DMEK, when performed within the first 6 to 8 postoperative weeks. However, rebubbled eyes may have lower ECD, which may be attributed to additional air bubble trauma and/or selection bias through more extensive manipulation during initial DMEK or higher risk of graft detachment in more complicated eyes.

The location of sites and effect of semiconductor diode trans‐scleral cyclophotocoagulation on the buphthalmic equine globe

To determine appropriate location and energy settings for trans-scleral cyclophotocoagulation (TSCPC) for buphthalmic equine globes. Eleven horses with a buphthalmic eye blinded by glaucoma presented for enucleation. Globe and corneal dimensions were measured via ultrasonography and calipers, and TSCPC was performed under general anesthesia immediately prior to enucleation. Part 1: In nine globes, sixty sites were lasered 4 mm posterior to the limbus in the dorsotemporal and ventrotemporal quadrants at settings of 1500 milliwatts and 1500 ms. Globes were processed and sectioned sagitally over the temporal aspect in two blocks, each with five histologic sections examined by light microscopy. A digital imaging system was used to determine the location and length of the pars plicata on one slide from each block. Part 2: Based on results in Part 1, two globes were measured and lasered using the same time and energy settings at the following distances posterior to the limbus: 8 mm dorsally, 6 mm dorsotemporally, 5 mm ventrotemporally, and 5 mm ventrally. Globe and corneal dimensions exceeded normal values in all globes. Part 1: In all nine globes, photocoagulation affected the anterior ciliary processes and iris base and in 8/9 coagulation of the pectinate ligaments was noted. Part 2: In both globes, coagulation was confined to the pars plicata. The previously recommended TSCPC sites are located too far anteriorly for a buphthalmic globe. Buphthalmic equine globes should have TSCPC performed at the following distances posterior to the limbus: 6-8 mm dorsally, 5-6 mm dorsotemporally, 4-5 mm ventrotemporally, and 4-5 mm ventrally.

Unilateral neonatal glaucoma (buphthalmos) with persistent hyperplastic primary vitreous

Leukocoria or white pupillary reflex in infancy or childhood is mostly associated with retinoblastoma (an intraocular malignancy). The possibility is increased if buphthalmos is also present, because non-malignant conditions like persistent hyperplastic primary vitreous (PHPV) usually have normal or small eyes. They rarely present with enlarged buphthalmic eye. Such was the condition in our neonate who presented with buphthalmos and leukocoria and was referred to us for management having been diagnosed with retinoblastoma. However, on investigating by imaging techniques (ultrasonography, Doppler and CT Scan) PHPV was confirmed, which is non-malignant. The patient was managed accordingly without enucleation. Even though rare, neonates or infants presenting with buphthalmos and leukocoria, should be investigated for non-malignant conditions like PHPV by imaging techniques to rule out a malignant condition – retinoblastoma.

Markedly asymmetric buphthalmos but without anisometropia in a girl with primary congenital glaucoma

Amblyogenic anisometropia is common in children with primary congenital glaucoma who have asymmetric buphthalmos. We report the case of a 6-year-old girl with markedly asymmetric buphthalmos but without anisometropia. Biometry confirmed that the more buphthalmic eye was longer than the contralateral eye and also had flatter keratometry.

A Novel Approach to the Management of Severe Facial Disfigurement in Neurofibromatosis Type 1

A 12-year-old girl with neurofibromatosis type 1 underwent subtotal anterior exenteration of a blind, unsightly, buphthalmic eye and orbital/eyelid plexiform neurofibroma. Simultaneously, a channeled Medpor orbital implant was positioned to reduce a meningoencephalocele resulting from severe sphenoid wing dysgenesis. Two-stage osseointegration was subsequently performed to permit secure fitting of an orbital prosthesis. This patient's cosmesis and social interaction were improved markedly with this surgical approach for disfiguring ocular, eyelid, and orbital disease due to neurofibromatosis type 1.

Immunohistochemical characterization of a malignant intraocular teratoid medulloepithelioma in a cockatiel

A 3-year-old cockatiel was presented for evaluation of a buphthalmic right eye (OD). The history included a traumatic event 5 months prior to presentation, and the referring veterinarian diagnosed cataract and secondary glaucoma. Computed tomography of the bird's orbital region revealed a large right orbital soft tissue mass that extended lateral to the orbital rim with obliteration of the globe without bone involvement. There was also no evidence of metastatic disease within the lungs or any abnormalities within the celomic cavity, therefore enucleation was recommended to achieve a histopathologic diagnosis and prognosis, and to palliate the clinical signs. Final diagnosis was malignant intraocular teratoid medulloepithelioma.

Combined Temporal Phacoemulsification and Pars Plana Vitrectomy for the Treatment of Cataract and Giant Retinal Tear in a Buphthalmic Eye

The standard approach to a three-port to pars plana vitrectomy is by placing the sclerotomies in the superotemporal and superonasal quadrant and the infusion port in the inferotemporal quadrant. This approach may be adjusted in selected cases that exhibit structural abnormalities of the globe at the superior site by placement of the sclerotomies in the temporal quadrants. We describe a case of a buphthalmic eye with a huge filtering bleb from previous glaucoma surgery that successfully underwent combined cataract and vitreoretinal surgery from a temporal approach for the repair of a giant retinal tear with cataract.

Choroidal Neurofibromatosis With Congenital Iris Ectropion and Buphthalmos: Relationship and Significance

We report a case of unilateral buphthalmos in neurofibromatosis-1 without the other classical characteristics of the François syndrome (triad of unilateral buphthalmos, homolateral eyelid plexiform neuroma, and homolateral facial hemihypertrophy) and emphasize the difficulties in early diagnosis. The painful buphthalmic right eye was enucleated at the age of 13 months. Histopathology demonstrated diffuse choroidal neurofibromatosis in association with congenital iris ectropion syndrome. Cutaneous manifestations of neurofibromatosis subsequently developed in the patient and stigmata of the disease were later identified in other asymptomatic family members.

Technique of direct goniotomy.

Surgery for congenital glaucoma requires precise visualization of angle structures of Schlemm canal. Transverse goniotomy requires a relatively clear cornea for controlled incision of angle structures. When an opaque cornea precludes this, ab externo trabeculotomy is a logical alternative. In severely buphthalmic eyes, finding Schlemm canal may be difficult because of distorted limbal anatomy. When trabeculotomy fails or Schlemm canal cannot be positively identified, direct goniotomy offers another surgical possibility. The technique of performing a goniotomy through a 60° limbal incision is described in detail. Angle structures are directly viewed and operated on through an open anterior chamber. Strict adherence to surgical technique and meticulous wound closure are essential to prevent postoperative complications. The approximately 50% cure rate justifies the potential risks inherent in opening a severely buphthalmic eye.

BUPHTHALMIA IN THE RABBIT: A TEST FOR EARLY DIAGNOSIS.

SummaryPathological and preclinical stages in the buphthalmic rabbit's eye can be distinguished by the degree of corneal cornification. This is determined by enumeration of cells removed from the intact anesthetized eye. Five normal strains and 2 buphthalmic strains were investigated. The buphthalmics had cell counts significantly higher than those of genetically normal animals. No significant differences were observed either between any of the control strains or between buphthalmic groups.

CONGENITAL BUPHTHALMOS

The following case is reported because of the favorable result that followed a severe injury and a stormy course in the only buphthalmic eye of a patient: History. —D. L., a white man aged 31, of Italian extraction, entered the ophthalmologic service of the Cook County Hospital on April 4, 1936. He gave a history of having been struck in the right eye by a finger fifteen hours previously. After the injury he became totally blind in his right eye. When the patient entered grammar school it was found that both of his eyes were larger than normal and that he had no vision in his left eye. The diagnosis was said to be bilateral congenital glaucoma. In 1911 a Lagrange type of operation was performed at the usual location on the right eye by Dr. Ben Witt Key, of New York. After this, the patient regained sufficient vision