Short GCG expansions in the PABP2 gene cause oculopharyngeal muscular dystrophy.

Autosomal dominant oculopharyngeal muscular dystrophy (OPMD) is an adult-onset disease with a world-wide distribution. It usually presents in the sixth decade with progressive swallowing difficulties (dysphagia), eyelid drooping (ptosis) and proximal limb weakness. Unique nuclear filament inclusions in skeletal muscle fibres are its pathological hallmark. We isolated the poly(A) binding protein 2 gene (PABP2) from a 217-kb candidate interval on chromosome 14q11 (B.B. et al., manuscript submitted). A (GCG)6 repeat encoding a polyalanine tract located at the N terminus of the protein was expanded to (GCG)8-13 in the 144 OPMD families screened. More severe phenotypes were observed in compound heterozygotes for the (GCG)9 mutation and a (GCG)7 allele that is found in 2% of the population, whereas homozygosity for the (GCG)7 allele leads to autosomal recessive OPMD. Thus the (GCG)7 allele is an example of a polymorphism which can act either as a modifier of a dominant phenotype or as a recessive mutation. Pathological expansions of the polyalanine tract may cause mutated PABP2 oligomers to accumulate as filament inclusions in nuclei.

Upper eyelid movements measured with a search coil during blinks and vertical saccades.

Upper eyelid movements were recorded in nine human subjects by mounting a miniature coil of wire directly on the eyelid and subjecting the search coil to a vertically directed alternating magnetic field. The metrics of blinks and lid movements accompanying saccades were described by "main sequence" relationships, linking maximum velocity to amplitude and duration to amplitude. In general, lid movements were faster than those reported previously in the literature, but there was considerable intersubject variability. On average, the main sequence relationships for blinks were independent of either starting lid position or whether the blinks were generated spontaneously, reflexively, or voluntarily. For the down phase of the average blink, both the maximum velocity and duration increased almost linearly with amplitude. The maximum velocity of the down phase was faster than that of the up phase. For lid movements accompanying vertical saccades, the maximum velocities in the up and down directions were similar and increased nonlinearly with amplitude, saturating at about 120 mm/sec (approximately 450 degrees/sec). Duration increased approximately linearly with amplitude. The down phases of blinks were much faster than those of saccade-related lid movements. By comparison, the maximum velocities of the up phase of blinks and of saccade-related lid movements were almost equal. The large intersubject variability suggests caution when using normative data to interpret abnormal lid motion for clinical purposes.

Eccrine sweat gland carcinoma of the eyelid with orbital involvement.

A 70-year-old man had a sweat gland carcinoma in his right upper eyelid that was slowly growing, but it clinically remained confined to the lid tissues for a period of 25 years. The tumor ultimately extended deeper into the orbit and invaded the sclera, the optic nerve sheath, and the ethmoidal sinuses. Histopathologic examination disclosed malignant features with a variety of cellular patterns. The results of electron microscopic studies confirmed the origin of the tumor from the eccrine sweat glands.

Necrobiotic xanthogranuloma of the eyelid.

Necrobiotic xanthogranuloma with paraproteinemia is characterized by multiple nodules or plaques that involve the periorbital area along with other parts of the body. A dysproteinemia due to an IgG paraprotein is associated with the condition; low serum complement, cryoglobulinemia, leukopenia, and hyperlipemia are also sometimes seen. Multiple myeloma is present in some cases. Two cases of necrobiotic xanthogranuloma with IgG monoclonal gammopathy were seen. Both initially had ocular symptoms and in the second case, the ocular manifestations have dominated the clinical picture. Histologically, these granulomas are characterized by collagen necrobiosis and by the presence of many foamy histiocytes and Touton giant cells. Because necrobiotic xanthogranuloma with monoclonal gammopathy frequently has prominent manifestations in the orbital region, may result in dysfunction of the eyelids or extraocular muscles, and is associated with potentially life-threatening systemic conditions, its recognition by the ophthalmologist is important.

Sebaceous carcinoma of the eyelid masquerading as superior limbic keratoconjunctivitis.

A 49-year-old woman had been treated for 18 months for superior limbic keratoconjunctivitis of the right eye. Pathologic examination of a biopsy specimen of the superior perilimbal conjunctiva disclosed intraepithelial carcinoma of sebaceous gland origin. Because of the extensive involvement of the conjunctival epithelium by tumor, a subtotal orbital exenteration was performed. To our knowledge, this is the first report of sebaceous carcinoma masquerading as superior limbic keratoconjunctivitis.

Bilateral blindness in temporal arteritis with skip areas.

A 73-year-old woman received systemic corticosteroids for suspected temporal arteritis after blindness developed in the right eye during the previous day. Because a right temporal artery biopsy specimen was reported as normal, a diagnosis of arteriosclerotic ischemic optic neuropathy was made and the corticosteroid therapy was discontinued. Two weeks later the patient rapidly lost vision in her left eye. A left temporal artery biopsy specimen showed granulomatous arteritis adjacent to normal artery (skip area). Deeper sections of the original right temporal artery biopsy specimen also demonstrated a small focus of granulomatous arteritis adjacent to normal artery. In patients with suspected temporal arteritis, numerous step sections of a long segment of temporal artery should be examined; if the results are normal, the contralateral temporal artery should be studied. A nonspecific inflammatory reaction within or adjacent to the artery should alert the pathologist to the possible presence of a nearby focus of granulomatous arteritis.

Interlocking Crawford triangles in frontalis suspension.

In Crawford's pattern of frontalis suspension, two bands are passed, one nasally and the other temporally, forming two base-down triangles with their apexes attached at the brow incisions. Over time, opposing vector forces in the center of the eyelid can cause "cheese-wiring" of the bands with resultant shortening of the inferior bases of both triangles and loosening of the suspensory loops. We modified the standard pattern by interlocking the bands centrally in the lid. A mathematical model was developed that demonstrates neutralization of these opposing forces, resulting in a symmetrical and flexible redistribution of the lifting forces. In support of this mathematical model, a retrospective analysis of 42 consecutive cases using this technique revealed good aesthetic results in terms of lid height, contour, and symmetry, with no important complications from this modification.

Pseudomonas aeruginosa scleritis.

In two patients Pseudomonas aeruginosa scleral infection led to ocular perforation. In one patient, a scleral abscess was identified anteriorly. A scleral perforation occurred at a more posterior focus, but the eye was salvaged with minimal residual visual function. In the other patient, perforation at the corneoscleral limbus occurred after initial corneal improvement with antibiotic therapy; histopathologic examination of the enucleated globe disclosed an abscess extending from the corneoscleral limbus to the equator superiorly.

Cryptophthalmos syndrome with bilateral renal agenesis.

We conducted a postmortem study of an infant with the abortive form of the cryptophthalmos syndrome. He had syndactyly and anal atresia and also showed features of Potter's (renal nonfunction) syndrome, including bilateral renal agenesis, pulmonary hypoplasia, and the typical facies. Histopathologic examination of both globes disclosed that the superior eyelid folds were partially replaced by skin that fused with the superior third of each cornea; there were also anomalies of the superior canaliculi and scarring of the corneas. We found no specific abnormality of the intraocular contents.

Pyogenic granuloma on a dermis fat graft in acquired anophthalmic orbits.

We treated exposure of the orbital implant with a dermis fat graft in two patients with an acquired anophthalmic orbit. During the first six postoperative months, a large polypoid tumor of the conjunctiva developed over the grafted tissue in each patient. Histologic examination of both lesions disclosed a pyogenic granuloma.

Lacrimal drainage system inflammatory masses from retained silicone tubing.

In two cases studied we found inflammatory masses of the lacrimal system associated with retained silicone material. We saw the first patient two years after a failed dacryocystorhinostomy. A mass of the superior punctum mimicking a lacrimal sac or canalicular neoplasm consisted of chronic granulomatous inflammation centered around retained silicone tubing. In the second patient, a foreign body giant cell inflammatory reaction occurred in the lacrimal sac in which there were retained knots of silicone tubing. We believed the inflammation in these patients to be caused by the knots and the cut ends of the silicone tubing present in the lacrimal drainage system.

Bilateral Candida albicans dacryocystitis with facial cellulitis.

Candida albicans rarely infects the lacrimal drainage system. This paper describes a case of bilateral C. albicans dacryocystitis following midfacial trauma. The patient presented with recurrent facial cellulitis and a fistula opening onto the cheek. The condition was controlled only after bilateral dacryocystorhinostomy along with amphotericin B therapy. This appears to be the first reported case in which the lacrimal sacs acted as a reservoir for microorganisms causing recurrent facial cellulitis.

Laser therapy of conjunctival papillomas.

Carbon dioxide (CO2) laser therapy was successfully used in the treatment of recurrent conjunctival papillomas in a 40-year-old man. Surgical excision, cryotherapy and immunotherapy with transfer factor and dinitrochlorobenzene had all been unsuccessful in eradicating the lesions. CO2 laser therapy should be considered as an alternative treatment for conjunctival papillomas refractory to other forms of therapy.

Mucinous eccrine sweat gland adenocarcinoma of the eyelid.

A firm, slow-growing cystic mass of the left upper eyelid developed in a 73-year-old man 5 years after a clinically diagnosed "sebaceous cyst" at the same site had been incised and drained. Histopathological examination disclosed a primary mucinous adenocarcinoma of eccrine sweat gland origin. The patient had no recurrence after 3.5 years of follow-up. Histochemical demonstration of sialomucin differentiates mucinous sweat gland carcinoma from other mucus-secreting adenocarcinomas, such as those arising from lacrimal gland tissue. Enzymatic histochemical analyses or ultrastructural studies are needed to distinguish between mucinous adenocarcinomas of eccrine origin and those of apocrine origin.

Streptococcal lid necrosis in previously healthy children.

Fulminant preseptal eyelid cellulitis developed in two previously healthy children, aged 17 months and 8 years, following minor trauma. Despite appropriate intravenous antibiotic therapy, lid necrosis with ulceration developed in both patients. In both cases group A beta-hemolytic Streptococcus was the causative agent. Spontaneous granulation of the ulcerated areas resulted in cicatricial defects, which in one case may require surgical correction. Neither child had a past history of susceptibility to infection. Group A beta-hemolytic Streptococcus has been known to cause lid gangrene, but almost all previously documented cases occurred in debilitated or elderly patients.

Effect of a topical anesthetic cream (EMLA) in reducing pain caused by infiltration of local anesthetic in eyelid surgery.

EMLA (eutectic mixture of local anesthetics) cream is a topical formulation of a mixture of lidocaine and prilocaine. It has been used to achieve local analgesia after application under an occlusive dressing. We carried out a double-blind randomized controlled clinical trial to assess the effect of 5% EMLA (25 mg/mL of lidocaine and of prilocaine) in reducing the pain caused by infiltration of local anesthetic in eyelid surgery. Pain was assessed by means of a modified visual analogue scale ranging from 0 (no pain) to 10 (excruciating pain) in 25 consecutive patients (average age 65 years) undergoing bilateral eyelid surgery. Clinical significance was defined as a difference in pain scores of 3 or more between EMLA and placebo. The mean pain scores for EMLA and placebo were 3.1 and 4.0 respectively, a nonsignificant difference. The EMLA preparation was found not to be clinically effective in reducing pain caused by infiltration of local anesthetic in eyelid surgery.

The orbicularis stripping operation for intractable blepharospasm: surgical results in eighteen patients.

The orbicularis stripping operation may be the only method of relieving the symptoms of essential blepharospasm when medical means and botulinum toxin injections fail.

Treatment of blepharospasm with medication, surgery and type A botulinum toxin.

A total of 39 patients with essential blepharospasm and 2 patients with hemifacial spasm were treated with one or more forms of therapy. All patients underwent neurologic and ophthalmic assessment to rule out ocular causes of blepharospasm. Thirty-six patients were given a trial of various medications. Only one patient was successfully treated: her condition was markedly improved with pimozide after benztropine mesylate, clonazepam and amantadine hydrochloride had failed to help. Patients who did not respond to drug therapy were offered the option of undergoing eyebrow-eyelid muscle stripping surgery. The six patients who underwent surgery showed considerable improvement; however, side effects such as frontal anesthesia, exposure keratitis, lagophthalmus, scarring and eyelid malposition occurred, and three of the six had residual spasm. At this point type A botulinum toxin became available. A total of 27 patients (26 who did not respond to drug therapy, including the 3 with residual spasm after surgery, and 1 previously untreated patient) received type A botulinum toxin injections. Most experienced rapid relief from their spasms. The beneficial effects lasted weeks to months, and there were no major side effects. Treatment with type A botulinum toxin appears to be a safe and effective means of temporarily relieving blepharospasm. The long-term results with repeated injections are yet to be determined.