Christine C. Nelson

Successful treatment of infantile Hemangiomas with Interferon-α-2b

PURPOSE Hemangiomas are benign tumors occurring in 10% of infants. A small percentage are complicated by blockage of vital structures, consumptive coagulopathy, or heart failure, resulting in a mortality of -20% of patients with complications. Here, we describe four infants with complicated hemangiomas responding to interferon-alpha-2b therapy. PATIENTS AND METHODS Four children with hemangiomas were treated with interferon-alpha-2b for complicating heart failure (1), visual impairment (2), or coagulopathy (1). Patients received interferon-alpha-2b alone or in conjunction with corticosteroid therapy over 2 to 9 months. Imaging studies and urinary basic fibroblast growth factor (bFGF) levels were used to monitor treatment response. RESULTS Three of four patients demonstrated involution of the hemangiomas with improvement in their coagulopathy or visual impairment. The fourth patient expired due to cardiac complications despite radiologic evidence of hemangioma involution. Side effects associated with interferon-alpha-2b treatment included elevated transaminases (2) and leukocytosis (2), which resolved upon completion of therapy. One patient developed mild gross motor delay (1), which improved after cessation of therapy. Decreased urinary bFGF levels correlated with hemangioma involution. CONCLUSION Interferon-alpha-2b therapy is an effective, well-tolerated treatment for complicated hemangiomas. Measurement of urinary bFGF levels may provide an objective method for monitoring treatment response.

A Histopathologic Study of 716 Unselected Eyes in Patients with Cancer at the Time of Death

To determine the frequency of ocular metastases in the general population, we conducted a prospective histopathologic study of 716 eyes obtained from patients who had malignant neoplasms at the time of death. Fifty-two patients had ocular metastases; all of these individuals had widespread metastases that contributed to their deaths. The overall incidence of ocular metastases among all fatal cases of cancer was 9.3%. Thirty-three of the 117 patients with various types of leukemia and four of the 60 patients dying with lymphoma had ocular involvement. The total incidence of ocular metastases in patients dying of all types of carcinoma was 4.0%. In the nine patients dying of sarcoma, no ocular metastases were detected. We estimate that about 22,000 patients who will die of cancer in the United States during 1983 will have ocular metastases.

Clinical heterogeneity in lymphoedema-distichiasis with FOXC2 truncating mutations

BACKGROUND Hereditary lymphoedema-distichiasis (LD) is an autosomal dominant disorder that classically presents as lymphoedema of the limbs, with variable age of onset, and extra aberrant growth of eyelashes from the Meibomian gland (distichiasis). Other major reported complications include cardiac defects, cleft palate, and extradural cysts. Photophobia, exotropia, ptosis, congenital ectropion, and congenital cataracts are additional eye findings. Recently, we reported that truncating mutations in the forkhead transcription family member FOXC2resulted in LD in two families. METHODS The clinical findings in seven additional families with LD, including the original family described by Falls and Kertesz, were determined and mutational analyses were performed. RESULTS Distichiasis was the most common clinical feature followed by age dependent lymphoedema. There is a wide variation of associated secondary features including tetralogy of Fallot and cleft palate. The mutational analyses identified truncating mutations in all of the families studied (two nonsense, one deletion, three insertion, and one insertion-deletion), which most likely result in haploinsufficiency ofFOXC2. CONCLUSIONS FOXC2mutations are highly penetrant with variable expressivity which is not explicable by the pattern of mutations.

The Effect of Omitting Botulinum Toxin From the Lower Eyelid in Blepharospasm Treatment

We randomly selected 26 patients with essential blepharospasm to receive either botulinum toxin or saline injection in their lower eyelids to evaluate the necessity of lower eyelid injection to relieve blepharospasm. As diplopia may occur from botulinum toxin injections for blepharospasm, most commonly from injection of the lower eyelid, and surgical relief of blepharospasm is often achieved by excision of only the upper eyelid protractors, omission of toxin from the lower eyelid seemed both desirable and possible. All patients received botulinum toxin in the upper eyelids, above the eyebrows, across the glabella, and near the lateral canthus. Thirteen of 15 patients who received saline in their lower eyelids had relief of spasm, with the same spasm-free interval as those who received toxin. We recommend avoiding injection of toxin in the medial two thirds of the lower eyelid in order to diminish the likelihood of diplopia from inferior oblique muscle paresis.

Development of Extraocular Muscles Requires Early Signals From Periocular Neural Crest and the Developing Eye

OBJECTIVES To identify and explain morphologic changes of the extraocular muscles (EOMs) in anophthalmic patients. METHODS Retrospective medical record review of patients with congenital anophthalmia, using magnetic resonance imaging and intraoperative findings to characterize EOM morphology. We then used molecular biology techniques in zebrafish and chick embryos to determine the relationships among the developing eye, periocular neural crest, and EOMs. RESULTS In 3 human patients with bilateral congenital anophthalmia and preoperative orbital imaging, we observed a spectrum of EOM morphologies ranging from indiscernible muscle tissue to well-formed, organized EOMs. Timing of eye loss in zebrafish and chick embryos correlated with the morphology of EOM organization in the orbit (eye socket). In congenitally eyeless Rx3 zebrafish mutants, or following genetic ablation of the cranial neural crest cells, EOMs failed to organize, which was independent of other craniofacial muscle development. CONCLUSIONS Orbital development is dependent on interactions between the eye, neural crest, and developing EOMs. Timing of the ocular insult in relation to neural crest migration and EOM development is a key determinant of aberrant EOM organization. Additional research will be required to study patients with unilateral and syndromic anophthalmia and assess for possible differences in clinical outcomes of patients with varied EOM morphology. CLINICAL RELEVANCE The presence and organization of EOMs in anophthalmic eye sockets may serve as a markers for the timing of genetic or teratogenic insults, improving genetic counseling, and assisting with surgical reconstruction and family counseling efforts.

Size variation of the lacrimal punctum in adults

This is the first reported study on accurate computerized measurements of lacrimal punctal size in normal adults. There was a wide variation found between patients. The lower lid puncta were consistently noted to be larger than those of the upper lids. This is clinically significant in dry-eye patients who may need to be treated with punctal plugs of various sizes.

A Comparison of Two Methods of Punctal Occlusion

We performed punctal occlusion by thermal cautery on 23 patients (45 sides, 90 puncta). One punctum on the right side was randomly assigned to deep cauterization of the punctum and vertical canaliculus, and the other punctum assigned to cauterization of the punctum only. The two treatments were assigned to the opposite puncta on the left side. One month after cauterization, the puncta that received deep cauterization were significantly more likely to have remained closed than those that received superficial cauterization (P less than .01). Survival analysis over a period of follow-up that exceeded one year after surgery, using time to examination because of a reopened punctum as the endpoint, indicated a long-term advantageous effect of deep over superficial cauterization.

Porous polyethylene as a spacer graft in the treatment of lower eyelid retraction.

PURPOSE An experimental study was performed to: 1) assess the tolerance and incorporation of porous polyethylene (Medpor) in the posterior lamella of the rabbit lower eyelid; 2) analyze the effect of implant thickness on incorporation; 3) investigate the ability of conjunctiva to grow over vascularized Medpor and; 4) determine the effects of Medpor surface modification on biocompatibility and fibrovascularization. METHODS In phase I, 10 rabbit eyelids were operated on to analyze the effects of implant thickness and to develop the surgical technique used in phase II of the study. In phase II, 20 lower eyelids of 10 rabbits received 0.85-mm-thick Medpor grafts, each rabbit receiving both an uncoated implant and one coated with an immobilized collagen. RESULTS There were no extrusions in phase II. with a postoperative follow-up from 14 to 17 weeks. Fourteen of 20 eyelids had full-thickness conjunctival incisions or excisions placed over the Medpor implant to determine the growth potential of conjunctiva over a vascularized implant. All but one eyelid showed complete defect coverage, occurring in as little as 3 days. Histopathology indicated complete Medpor fibrovascularization as early as 4 weeks after implantation. Because neither coated nor uncoated implants extruded in phase II, no conclusions can be drawn regarding the efficacy of Medpor surface modification. CONCLUSION Medpor was well tolerated in this soft tissue application, and it offers advantages over other graft materials.

Mutation of the FOXC2 gene in familial distichiasis

OBJECTIVE To examine the FOXC2 gene in a family with hereditary distichiasis. BACKGROUND Distichiasis, ie, a second row of eyelashes arising from the meibomian glands of the eyelids, can be inherited either alone (Online Mendelian Inheritance in Man [OMIM] no. 126300) or, more commonly, as part of the lymphedema-distichiasis (LD) syndrome (OMIM no. 153400). More than 45 families with mutations in the FOXC2 gene and LD have been described. Both lymphedema and distichiasis are highly penetrant. Distichiasis without lymphedema is not commonly seen. METHODS We examined three generations of a family (N = nine members) with hereditary distichiasis but without lymphedema or other features of LD syndrome. The FOXC2 gene was polymerase chain reaction--amplified from genomic DNA from all family members and examined for mutations. RESULTS Clinical examination showed distichiasis of all four lids in two affected family members across two generations. There were no other consistent ophthalmologic abnormalities in the family. A cytosine-to-adenine transversion was identified in DNA from affected study participants at nucleotide position 1076, which would be predicted to cause truncation of the protein at codon 359. This change was not observed in any of the nine unaffected family members participating. CONCLUSIONS This finding suggests that hereditary distichiasis and LD may not be separate genetic disorders but different phenotypic expressions of the same underlying disorder. Ophthalmologists should be aware that LD may present as distichiasis alone and counsel and refer their patients appropriately.

Invasive squamous cell carcinoma of the conjunctiva presenting as necrotizing scleritis with scleral perforation and uveal prolapse

A 64-year-old white man presented with necrotizing scleritis with scleral perforation and uveal prolapse. Pathologic examination revealed squamous cell carcinoma of the conjunctiva invading adjacent corneal stroma and ciliary body. Invasive squamous cell carcinoma of the conjunctiva is uncommon, and intraocular invasion has rarely been reported in the literature.