Fouad R. Zakka

Intraocular Pressure Measurement by Radio Wave Telemetry

PURPOSE To determine the biocompatibility of a new wireless intraocular pressure (IOP) transducer (WIT) in rabbit eyes and to correlate its measurements with other pressure-measuring devices. METHODS The WIT is a ring-shaped intraocular device that allows wireless IOP measurements through radiofrequency. It was implanted into six eyes of New Zealand White rabbits after extracapsular lens extraction. A sham rabbit eye with no transducer implanted was used as a control. The animals were observed and examined by microscopy at various intervals up to 25 months after surgery. IOP was measured at various intervals by pneumotonometry, tonometry, WIT, and manometry. The data from the various devices were compared and analyzed for reproducibility. Two eyes were enucleated at 5.5 and 20 months after implantation and analyzed by histology. RESULTS The WIT appears to be well tolerated in the rabbit eye, with no evidence of significant inflammation or scar formation by microscopic in vivo examination. Histology did not reveal intraocular inflammation or membrane formation. Repeated IOP measurements with pneumotonometry, tonometry, and the WIT resulted in SDs of 2.70 mm Hg, 3.35 mm Hg, and 0.81 mm Hg, respectively. The concordance between the WIT and direct manometry measurements was high. A downward drift in IOP measured by the WIT was noted in three rabbits, necessitating recalibration. CONCLUSIONS The WIT is well tolerated by the rabbit eye. Its measurements are reproducible and in close concordance with manometry. A downward IOP drift warrants further investigation.

Systemic therapy with conventional and novel immunomodulatory agents for ocular inflammatory disease.

Ocular inflammatory disease is the third leading cause of blindness in the United States. In addition to the conventional immunomodulatory agents, which include antimetabolites, alkylating agents, and antibiotics such as cyclosporine, many of which have been used in the treatment of this disease for decades, several new treatment modalities have emerged within the past 10 years. We review in detail the characteristics, safety, and efficacy of the conventional immunomodulators, the more novel agents such as the biologics, and investigational drugs that appear promising in the treatment of ocular inflammatory disease.

Biocompatibility and biofilm inhibition of N,N-hexyl,methyl-polyethylenimine bonded to Boston Keratoprosthesis materials

The biocompatibility and antibacterial properties of N,N-hexyl,methyl-polyethylenimine (HMPEI) covalently attached to the Boston Keratoprosthesis (B-KPro) materials was evaluated. By means of confocal and electron microscopies, we observed that HMPEI-derivatized materials exert an inhibitory effect on biofilm formation by Staphylococcus aureus clinical isolates, as compared to the parent poly(methyl methacrylate) (PMMA) and titanium. There was no additional corneal epithelial cell cytotoxicity of HMPEI-coated PMMA compared to that of control PMMA in tissue cultures in vitro. Likewise, no toxicity or adverse reactivity was detected with HMPEI-derivatized PMMA or titanium compared to those of the control materials after intrastromal or anterior chamber implantation in rabbits in vivo.

A reappraisal of eyelid eccrine and apocrine hidrocystomas: microanatomic and immunohistochemical studies of 40 lesions.

PURPOSE To establish reliable criteria for diagnosing eyelid eccrine and apocrine hidrocystomas. DESIGN Retrospective clinicopathologic and immunohistochemical study. METHODS Twenty-two specimens of normal portions of eyelids were evaluated to establish the distribution and microanatomy of eccrine and apocrine glands. Immunostaining for cytokeratin 7 (CK7), gross cystic disease fluid protein-15 (GCDFP-15), alpha-smooth muscle actin (α-SMA), epithelial membrane antigen (EMA), and carcinoembryonic antigen (CEA) was performed on these tissues and on 40 lesions in 33 patients diagnosed with eccrine or apocrine hidrocystomas by unaided light microscopy. RESULTS Eccrine glands were not present in the eyelid margins, the lower half of the upper eyelid pretarsal skin, or the pretarsal lower eyelid skin. Apocrine glands were restricted to the eyelid margins and canthi where the cysts were located. GCDFP-15, CK7, and α-SMA immunoreacted with the eccrine secretory coils but not their ducts; apocrine gland secretory spirals also stained positively for these markers throughout their extended courses, but not their short terminal ducts. Positivity was found in 37 of 40 hidrocystomas for α-SMA and 19 for GCDFP-15; lesions tested for CK7 displayed positivity. CONCLUSIONS Alpha-SMA-, CK7-, and/or GCDFP-15-positive apocrine hidrocystomas were the only type discovered in this series and arose from glandular secretory spirals within the marginal, perimarginal, or canthal skin. Three lesions did not stain for α-SMA, initially suggesting an absent myoepithelium and therefore an eccrine ductal origin; they manifested CK7 positivity, however, another characteristic of the apocrine secretory spiral but not ducts. Our findings disprove the contention that eccrine predominate over apocrine hidrocystomas in the eyelids.

Giant Dacryocystomucopyocele in an Adult: A Review of Lacrimal Sac Enlargements With Clinical and Histopathologic Differential Diagnoses

Dacryocystocele is an umbrella term that refers to any diffuse, centrifugal enlargement of the lacrimal sac that results from combined proximal and distal obstructions in the tear drainage system. In adults, the presence of mucus in the cysts contents leads to the modified term of dacryocystomucocele. If infection supervenes, which almost always occurs in protracted cases and adds the clinical dimension of a dacryocystitis, then a dacryocystomucopyocele is created. Dacryocystocele and its congeners are much rarer in adults than in children. We describe a 95-year-old woman with an acquired, enormous dacryocystomucopyocele, larger than any previously reported, that developed over 25 years and produced globe displacement with an associated conspicuous enlargement of the nasolacrimal duct. The aspirated sac fluid was mucopurulent and harbored low-virulence bacterial organisms of the Prevotella and Petosteptococcus species. In infants, dacryocystoceles are transitory as the result of spontaneously reversible factors. In adults, secondary proximal irreversible fibrotic strictures or bony changes around the nasolacrimal duct typically arise from chronic inflammation or low grade infection. Other possible causations of duct obstruction, in addition to florid mucosal edema, include encroachment on the duct by enlarged contiguous ethmoid air cells; a sinus mucocele or sinusitis; idiopathic, post-traumatic or dysplastic bony remodeling of the wall of the duct; and a neoplasm-all of which require some form of surgical intervention, typically dacryocystorhinostomy. The differential diagnosis of medial canthal swellings centered on the lacrimal sac spans malformations, diverticula, dermoid/epidermoid cysts, sac inflammations/infections causing swelling without generalized sac enlargement, encephaloceles and primary epithelial tumors, as well as extrinsic tumors impinging on the sac.

Bacterial and mucopeptide concretions of the lacrimal drainage system: an analysis of 30 cases.

Purpose: To demonstrate the histopathologic characteristics of different types of lacrimal drainage system concretions with clinical correlations. Methods: Thirty lacrimal drainage system concretions submitted to the Cogan Eye Pathology Laboratory at the Massachusetts Eye and Ear Infirmary over a 2-year period were reviewed. Concretions were studied in detail using their histopathologic staining features as revealed with hematoxylin and eosin, Gomori methenamine silver, periodic acid-Schiff, iron stain, and Brown-Hopps tissue gram stain. A separate retrospective chart review was conducted for each patient to identify any clinical correlations. Results: Two major forms of concretions were identified histopathologically: mucopeptide (7) and bacterial (20). Mucopeptide concretions were found exclusively within the lacrimal sac, while bacterial concretions were found chiefly in the canaliculus. A third category of “mixed” concretions with substantial mucopeptide and bacterial characteristics comprised 3 specimens. Bacterial concretions consisted of large matted masses of filamentous, presumed Actinomyces organisms that were easily identified with the Grocott’s methenamine silver stain; they were frequently cocolonized at their edges with coccal bacterial forms. Mucopeptide concretions were generally devoid of cellular elements and were composed of broad bland whorls of diffusely eosinophilic, acellular, periodic acid-Schiff-positive material punctuated by lacunae. They were often cocolonized by small numbers of bacterial cocci and occasional fungi. Culture results disclosed low virulence species. All 3 types of concretions predominated in women. Patients with bacterial concretions frequently had dry eye symptoms. Conclusions: The 2 major types of lacrimal system concretions differ in their primary location and histopathologic composition. Further characterization may lead to an understanding of the mechanisms for their formation. Mucopeptide concretion is more appropriate than terms such as “dacryolith” and “mucolith,” and bacterial concretion is a more appropriate term than “canaliculith,” because of the absence of significant calcium or stone-like density in these masses.

Influence of Aromatase Absence on the Gene Expression and Histology of the Mouse Meibomian Gland

PURPOSE We hypothesize that aromatase, an enzyme that controls estrogen biosynthesis, plays a major role in the sex-related differences of the meibomian gland. To begin to test this hypothesis, we examined the influence of aromatase absence, which completely eliminates estrogen production, on glandular gene expression and histology in male and female mice. METHODS Meibomian glands were obtained from adult, age-matched wild-type (WT) and aromatase knockout (ArKO) mice. Tissues were processed for histology or the isolation of total RNA, which was analyzed for differentially expressed mRNAs by using microarrays. RESULTS Our results show that aromatase significantly influences the expression of more than a thousand genes in the meibomian gland. The nature of this effect is primarily sex-dependent. In addition, the influence of aromatase on sex-related differences in gene expression is predominantly genotype-specific. However, many of the sex-related variations in biological process, molecular function, and cellular component ontologies, as well as in KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways, are remarkably similar between WT and ArKO mice. The loss of aromatase activity has no obvious effect on the histology of meibomian glands in male or female mice. CONCLUSIONS Our findings demonstrate that aromatase has a significant impact on gene expression in the meibomian gland. The nature of this influence is sex-dependent and genotype-specific; however, many of the sex-related variations in gene ontologies and KEGG pathways are similar between WT and ArKO mice. Consequently, it appears that aromatase, and by extension estrogen, do not play a major role in the sex-related differences of the mouse meibomian gland.

Newborn primary congenital glaucoma: Histopathologic features of the anterior chamber filtration angle

We present histopathologic findings that have not been previously reported as associated with abnormalities of the anterior chamber angle underlying newborn primary congenital glaucoma as a distinct entity. The major histopathologic findings were partial absence and retrodisplacement of Schlemms canal, hypoplasia of the trabecular meshwork, broad attachment of ciliary muscle to the meshwork, and anterior insertion of hypoplastic iris with the formation of a pseudomembrane. These profound anatomic derangements explain why goniosurgery is frequently unsuccessful in cases of newborn glaucoma.

Eyelid basal cell carcinoma developing in an epidermoid cyst: a previously unreported event.

A 72-year-old woman presented with a 3 × 2 × 1-mm right lower eyelid micronodular, whitish solid lesion at the nasal eyelid margin that had caused madarosis. Local excision led to the microscopic discovery of 2 epidermoid cysts, one of which harbored a basal cell carcinoma arising from its orthokeratinizing squamous cell lining. Poral openings indicated that the cysts represented follicular infundibular ectasias. BER-EP4-positive immunostaining confirmed the basal cell nature of the neoplasm. This is the first example in the eyelid of an epidermoid cyst displaying malignant transformation. No matter how innocent they may appear, all small cystic or noncystic eyelid lesions should be submitted for pathologic evaluation.

Angiomyofibroma of the orbit: a hybrid of vascular leiomyoma and cavernous hemangioma.

Purpose: The aim of this study was to describe a novel primary orbital vascular tumor combining elements of a vascular leiomyoma (angioleiomyoma) and a cavernous hemangioma. Methods: A critical review of clinical records, diagnostic tests, and radiographic studies combined with histopathologic evaluation with standard and special histochemical staining and immunohistochemical investigations was conducted. Results: A 44-year-old man slowly developed 5 mm of well-tolerated relative right proptosis with minimal motility disturbance and no visual decline. Computed tomography and magnetic resonance imaging demonstrated a medial and intraconal rounded mass that perfused slowly and whose anterior surface was well circumscribed. At surgery, the tumor was solid and pink with intersecting white bands and densely attached to surrounding normal tissues. The most adherent apical portion of the mass was left behind after subtotal excision. Histopathologically, only a partial pseudocapsule was discovered. The tumor was composed of cavernous channels, capillary zones, compressed lumens with linear strands of endothelium, and collections of muscular veins devoid of an elastica. Striking smooth muscle actin positivity was identified in disorganized masses of smooth muscle cells in the intervascular spaces and around the cavernous vascular units; these myocytes were intermixed with bundles of interstitial keloidal collagen. The endothelium was CD31 and CD34 positive for vascular endothelium and D2-40 negative for lymphatic endothelium. Conclusions: The authors have classified this hybrid tumor an angiomyofibroma with low neoplastic potential and features of a malformation. It is a composite variant of cavernous hemangioma associated with a conspicuous proliferation of anomalous disorganized smooth muscle cells (leiomyoma). Most of the lesion lacked a pseudocapsule, which impeded surgical delivery. Incomplete excision is recommended in such cases as preferable to the complications that could ensue from overly aggressive efforts at complete removal, particularly at the orbital apex. Supporting this position is the observation that incompletely excised cavernous hemangioma generally does not recur.