David T. Tse

Ophthalmic complications of sinus surgery

Seven patients with orbital complications of sinus surgery seen over a 10-year period are reported. Severe intraoperative orbital hemorrhage occurred in three patients while undergoing external or intranasal ethmoidectomy. In one patient, an avulsed anterior ethmoidal artery was identified as the source of bleeding, whereas in two others bleeding was due to snaring of orbital tissues. In two of these three cases, intraoperative recognition and prompt treatment of the expanding hematoma resulted in preservation of vision. Motility disturbances due to extraocular muscle injury occurred in two patients after intranasal ethmoidectomy and in one patient after a Caldwell-Luc procedure. Bilateral blindness resulted from transection of both optic nerves in one patient during bilateral intranasal endoscopic ethmoidectomies. Recommendations for prevention, intraoperative recognition, and management of such ophthalmic complications of sinus surgery are given.

Ocular-adnexal Lymphoid Tumors: A Clinicopathologic and Molecular Genetic Study of 77 Patients

PURPOSE To determine whether molecular genetic analysis of ocular-adnexal lymphoid tumors, combined with histopathology and tumor location, is helpful in predicting which patients will develop systemic lymphoma. METHODS A combined retrospective and prospective study of 77 patients with ocular-adnexal lymphoid tumors was performed. The tumors were subdivided into conjunctival, orbital, and eyelid lesions, and all were studied using both routine histopathology and molecular genetic analysis. RESULTS Most lesions (70%) were small cell lymphomas of the mucosa-associated lymphoid tissue type, and the majority of tumors (90%) contained monoclonal or oligoclonal populations of lymphocytes discovered on molecular genetic analysis. Additionally, 72% of tumors exhibiting clonality had more than one gene rearrangement. Fifty-three percent of patients developed extraocular lymphoma sometime during the course of their disease. Patients with gene rearrangements on Southern blot hybridization had a 52% incidence of nonocular disease, compared with 63% of those without rearrangements. Patients with conjunctival tumors had a 37.5% incidence of nonocular disease, those with orbital tumors had a 54% incidence, and those with eyelid tumors had a 100% incidence of nonocular lymphoma. Only two patients died as result of systemic lymphoma. CONCLUSIONS Most ocular-adnexal lymphoid tumors are lymphomas of the mucosa-associated lymphoid tissue type. The majority of tumors exhibit gene rearrangements on molecular genetic analysis, and this technique was not helpful in predicting which patients would develop nonocular lymphoma. Tumor location did have predictive value: Conjunctival lesions had the lowest incidence of nonocular lymphoma, and lid lesions had the highest incidence. Even with disseminated disease, most patients have a favorable prognosis with treatment.

Involutional entropion repair with fornix sutures and lateral tarsal strip procedure

Purpose To evaluate the long-term effectiveness of fornix suture placement combined with a lateral tarsal strip procedure in correcting involutional entropion. Published reports regarding various surgical techniques and results are reviewed. Methods This retrospective study reviewed 119 patients with involutional lower eyelid entropion who underwent surgical repair between January 1987 and May 1999 at the Bascom Palmer Eye Institute. Exclusion criteria included follow-up duration of less than 6 months, previous lower eyelid blepharoplasty, previous conjunctival surgery other than chalazion removal, or cicatricial entropion. The three surgical subsets were (1) combined lateral tarsal strip and fornix sutures; (2) fornix sutures alone; and (3) lateral tarsal strip procedure alone. The chart review was complemented by a telephone questionnaire to assess the long-term clinical outcome, complications, and patient satisfaction. Results One hundred fifty-two eyelids in 119 patients were included. One hundred twenty-five eyelids had combined surgery (lateral tarsal strip with fornix sutures), 9 eyelids had only fornix suture repair, and 18 eyelids had repair with only the lateral tarsal strip procedure. The recurrence rate in these three surgical subsets was 1.6%, 33%, and 22%, respectively, with average follow-up of 36 months. One case of incisional cellulitis was encountered. Postoperative ectropion was not seen in the group having the combined lateral tarsal strip and fornix suture procedure. Conclusions Suture advancement of the lower eyelid retractors in conjunction with a lateral tarsal strip procedure is a simple, quick, physiologic, and effective approach in achieving long-lasting correction for involutional entropion.

Safety and Effects of the Vector for the Leber Hereditary Optic Neuropathy Gene Therapy Clinical Trial

IMPORTANCE We developed a novel strategy for treatment of Leber hereditary optic neuropathy (LHON) caused by a mutation in the nicotinamide adenine dinucleotide dehydrogenase subunit IV (ND4) mitochondrial gene. OBJECTIVE To demonstrate the safety and effects of the gene therapy vector to be used in a proposed gene therapy clinical trial. DESIGN AND SETTING In a series of laboratory experiments, we modified the mitochondrial ND4 subunit of complex I in the nuclear genetic code for import into mitochondria. The protein was targeted into the organelle by agency of a targeting sequence (allotopic expression). The gene was packaged into adeno-associated viral vectors and then vitreally injected into rodent, nonhuman primate, and ex vivo human eyes that underwent testing for expression and integration by immunohistochemical analysis and blue native polyacrylamide gel electrophoresis. During serial follow-up, the animal eyes underwent fundus photography, optical coherence tomography, and multifocal or pattern electroretinography. We tested for rescue of visual loss in rodent eyes also injected with a mutant G11778A ND4 homologue responsible for most cases of LHON. EXPOSURE Ocular infection with recombinant adeno-associated viral vectors containing a wild-type allotopic human ND4 gene. MAIN OUTCOMES AND MEASURES Expression of human ND4 and rescue of optic neuropathy induced by mutant human ND4. RESULTS We found human ND4 expressed in almost all mouse retinal ganglion cells by 1 week after injection and ND4 integrated into the mouse complex I. In rodent eyes also injected with a mutant allotopic ND4, wild-type allotopic ND4 prevented defective adenosine triphosphate synthesis, suppressed visual loss, reduced apoptosis of retinal ganglion cells, and prevented demise of axons in the optic nerve. Injection of ND4 in the ex vivo human eye resulted in expression in most retinal ganglion cells. Primates undergoing vitreal injection with the ND4 test article and followed up for 3 months had no serious adverse reactions. CONCLUSIONS AND RELEVANCE Expression of our allotopic ND4 vector in the ex vivo human eye, safety of the test article, rescue of the LHON mouse model, and the severe irreversible loss of visual function in LHON support clinical testing with mutated G11778A mitochondrial DNA in our patients.

Radiation therapy for local control of eyelid sebaceous cell carcinoma: report of two cases and review of the literature.

Purpose Because of previous reports of increased rate of recurrence and mortality after radiation therapy, eyelid sebaceous cell carcinoma has been considered radioresistent. Recent reports of success with primary radiation therapy have been attributed to advancements in irradiating technology and technique. Two cases of eyelid sebaceous cell carcinoma successfully treated with radiation therapy are reported. The techniques used are compared with the techniques described in previous reports, and factors favoring successful treatment are reevaluated. Methods Case series and review of the literature. Two cases of eyelid sebaceous cell carcinoma that underwent radiation therapy are described. Both patients were offered, but refused, surgical excision. One patient received 69 Gy combined superficial and megavoltage x-ray irradiation to the left lower eyelid. The second patient received 59 Gy megavoltage electron beam irradiation to the right upper eyelid. A review of the literature was performed, and Fisher’s exact test analysis was used to compare the results of all reported cases treated with ≤55 Gy with those treated with >55 Gy. Results In both cases, the tumor responded to radiation therapy. One patient died 39 months after treatment, of myocardial infarction. The second patient is without clinical evidence of tumor recurrence 46 months after treatment. Fisher’s exact test showed an advantage to patients treated with >55 Gy radiation (p = 0.05). Conclusion Radiation therapy with an appropriate delivery system is effective as a curative treatment for eyelid sebaceous cell carcinoma when >55 Gy of radiation dose is delivered. It should be considered for patients seeking an alternative to surgical excision.

Long-term outcomes of neoadjuvant intra-arterial cytoreductive chemotherapy for lacrimal gland adenoid cystic carcinoma.

PURPOSE To compare the long-term outcomes after intra-arterial cytoreductive chemotherapy (IACC) with conventional treatment for lacrimal gland adenoid cystic carcinoma (ACC). DESIGN Retrospective case series. PARTICIPANTS Nineteen consecutive patients treated with IACC, followed by orbital exenteration, chemoradiotherapy, and intravenous chemotherapy. INTERVENTIONS Analyses of the histologic characteristics of biopsy specimens, extent of disease at the time of diagnosis, diagnostic surgical procedures, incidence of locoregional recurrences or distant metastases, disease-free survival time, response to IACC, tumor margins at definitive surgery, and toxicity and complications. MAIN OUTCOME MEASURES Disease relapse, disease-free survival, and chemotherapeutic complications. RESULTS Eight patients with an intact lacrimal artery had significantly better outcomes for survival (100% vs. 28.6% at 10 years), cause-specific mortality, and recurrences (all P = 0.002, log-rank test) than conventionally treated patients from the University of Miami Miller School of Medicine. These 8 patients (group 1) had cumulative 10-year disease-free survival of 100% compared with 50% for 11 patients (group 2) who had an absence of the lacrimal artery or deviated from the treatment protocol (P = 0.035) and 14.3% for conventionally treated patients (P<0.001). Likewise, group 2 was associated with lower cause-specific mortality than the institutional comparator group (P = 0.038). Prior tumor resection with lateral wall osteotomy, delay in IACC implementation or exenteration, and failure to adhere to protocol are risk factors for suboptimal outcomes. CONCLUSIONS Neoadjuvant IACC seems to improve overall survival and decrease disease recurrence. An intact lacrimal artery, no disruption of bone barrier or tumor manipulation other than incisional biopsy, and protocol compliance are factors responsible for favorable outcomes. The chemotoxicity complication rate is limited and manageable.

Periocular atypical mycobacterial infections

OBJECTIVE To examine the clinical characteristics and management of periocular infections caused by atypical mycobacteria. DESIGN Retrospective, noncomparative case series. PARTICIPANTS Six patients were identified with periocular atypical mycobacterial infections: four with Mycobacterium chelonae and two with Mycobacterium fortuitum. INTERVENTION The treatment of these infections included removal of the foreign bodies with debridement of the lesions. Specimens were sent for histopathologic examination, routine cultures, and fresh tissue for culture after homogenization. MAIN OUTCOME MEASURES A retrospective review of culture-proven atypical mycobacterial infections involving the periocular tissues was performed. Charts were reviewed for age, gender, infectious organism, medical history, surgical history, presenting symptoms, clinical features, and treatment. RESULTS Four associations with infection were identified in these patients: immunosuppression, nasolacrimal duct obstruction, the presence of a foreign body, and a history of recent surgery. All six of the patients had at least one of these associations and five of the patients had at least two. Clinical characteristics that may distinguish atypical mycobacterial infections from acute bacterial infections include subacute presentation, firm nodular lesions, mild erythema, mild tenderness, and minimal purulent discharge. All patients had resolution of their infections after debridement and several weeks of systemic antibiotic therapy guided by susceptibility testing. CONCLUSIONS Periocular atypical mycobacterial infections are uncommon. The clinical history and examination can raise the suspicion of this infection by revealing the clinical characteristics of these infections. Treatment includes removal of foreign bodies, debridement, and long-term systemic antibiotic therapy.

Sebaceous cell carcinoma of the eyelid and the human immunodeficiency virus.

Purpose Patients infected with the human immunodeficiency virus (HIV) are at increased risk for developing malignancies, which are acquired at a younger age and are more aggressive. Sebaceous cell carcinoma is a rare eyelid tumor typically occurring in the seventh decade of life. We report two cases of sebaceous cell carcinoma in young HIV-infected patients. Methods Case series and review of the literature. We describe two HIV-infected patients with sebaceous cell carcinoma of the eyelid and caruncle. The first patient was a 36-year-old woman with a 9-month history of an enlarging right lower eyelid mass. The second patient was a 34-year-old man with a 6-month history of an enlarging right caruncular mass. Results Biopsy showed both masses to be sebaceous cell carcinoma. The first patient underwent Mohs’ micrographic excision of the lesion followed by reconstruction of the full-thickness eyelid defect with a combination of tarsoconjunctival and myocutaneous advancement flaps. The second patient underwent exenteration because of orbital involvement. Conclusion Sebaceous cell carcinoma should be considered for any suspicious eyelid lesion in young HIV-infected patients.

Optic Canal Decompression: A Cadaveric Study of the Effects of Surgery

Purpose: To simulate a transphenoidal medial optic canal decompression and determine the anatomic effect on the optic nerve. Methods: A medial optic canal decompression was performed on 5 cadaveric optic canals within 12 hours of death. Two canals were decompressed under direct visualization and 3 were decompressed by a transphenoidal endoscopic approach. The optic canal was subsequently removed en bloc, beginning at the annulus of Zinn and extending to the optic chiasm. Each specimen was processed and examined grossly. Serial coronal step sections of the entire length of the intracanalicular optic nerve were assessed histologically. Results: Microscopic examination of the intracanalicular portion of optic nerve revealed incision in an extraocular muscle at the annulus, incomplete bone removal, fraying of the dural sheath, incomplete dural/arachnoid release, and incision in the pia and optic nerve. Conclusions: Transphenoidal medial wall decompression of the optic nerve canal with dural sheath opening may induce physical damage to the nerve. Any hypothetical value in dural-arachnoid sheath opening must be weighed against the potential for harm to the optic nerve caused by the surgical intervention.

Microdissection Genotyping Analysis of the Effect of Intraarterial Cytoreductive Chemotherapy in the Treatment of Lacrimal Gland Adenoid Cystic Carcinoma

PURPOSE To investigate the feasibility of integrating molecular analysis into standard histopathology for lacrimal gland adenoid cystic carcinoma (ACC), and to gain insights into the molecular pathogenesis of this tumor and its response to intraarterial cytoreductive chemotherapy (IACC) that is of clinical use. DESIGN A retrospective, comparative case series. METHODS setting: Institutional. patient population: Nine consecutive patients with lacrimal gland ACC were treated with IACC, followed by orbital exenteration and chemoradiotherapy. This case series was compared with a series of seven patients treated by conventional local therapies. intervention procedure: Gene analysis was performed on microdissected tissue samples. Mutational allelotyping targeting nine genomic loci was performed with 15 polymorphic microsatellite markers situated in proximity to known tumor suppressor genes serving as markers for the presence of gene deletion. main outcome measure: A fractional mutation index was used to compare the acquired mutational load between different tumors having nonidentical patterns of microsatellite informativeness. RESULTS Allelic imbalance (loss of heterozygosity [LOH]) for microsatellite markers at 1p36 was the single most common site affected by imbalance in this series, followed by LOH in temporal sequence involving 9p21, 22q12, 10q23, and 9q22. CONCLUSIONS Microdissection genotyping holds promise as a clinical tool in integrating molecular analysis into standard histopathology to advance the understanding of lacrimal gland ACC tumorigenesis. A unique time course for temporal mutation acquisition in ACC is proposed, consisting of 1p36 loss first. Allelic loss for microsatellite markers at 1p36 may be a common as well as an early event in ACC formation and progression.