Evelyn A. Paysse

Response of retinoblastoma with vitreous tumor seeding to adenovirus-mediated delivery of thymidine kinase followed by ganciclovir

PURPOSE To evaluate the feasibility and safety of adenovirus-mediated gene therapy as a treatment for tumor seeds in the vitreous of children with retinoblastoma. PATIENTS AND METHODS An Institutional Biosafety Committee-, Institutional Review Board-, Recombinant DNA Advisory Committee-, and US Food and Drug Administration-approved phase I study used intrapatient dose escalation of adenoviral vector containing a herpes simplex thymidine kinase gene (AdV-TK) followed by systemic administration of ganciclovir to treat bilateral retinoblastoma with vitreous tumor seeding refractory to standard therapies. Vitreous tumor seeds were treated by intravitreous injection of AdV-TK adjacent to disease sites. Each injection was followed by ganciclovir delivered intravenously every 12 hours for 7 days. RESULTS Eight patients with vitreous tumor seeds were enrolled. One patient who was treated with 10(8) viral particles (vp) had resolution of the tumor seeds around the injection site. The seven patients who were treated with doses > or = 10(10) vp had resolution of their vitreous tumor seeds documented by fundoscopy. Toxicity included mild inflammation at 10(10) vp and moderate inflammation, corneal edema, and increased intraocular pressure at 10(11) vp. One patient was free of active vitreous tumor seeds 38 months after therapy. There has been no evidence of extraocular spread of tumor along the needle tract in any patient. CONCLUSION AdV-TK followed by ganciclovir can be administered safely to children with retinoblastoma. Suicide gene therapy may contribute to the treatment of children with retinoblastoma tumor seeds in the vitreous, a resistant complication of retinoblastoma.

Impact of large angle horizontal strabismus on ability to obtain employment.

OBJECTIVE To determine if large angle esotropia and exotropia could impact a persons ability to obtain employment. DESIGN Laboratory experiment. PARTICIPANTS Seventy-nine respondents unaware of the purpose of the study. METHODS Photographs of two men and two women were digitally altered to create photographs of the same individual in an orthotropic, esotropic, and exotropic state. The photographs were then randomly affixed to similarly qualified job resumes. The 79 study respondents, unaware of the purpose of the study, were asked to (1) rate each individual applicant on selected job qualification variables, and (2) rank the applicants against each other in order of hiring preference. MAIN OUTCOME MEASURES Individual applicant rating and hiring preference scores. RESULTS Women with normal ocular alignment received greater hiring preference scores than did strabismic women (P = 0.007). No difference in hiring preference scores was noted between strabismic and non-strabismic male applicants (P = 0.47). CONCLUSIONS Large angle horizontal strabismus appeared to be vocationally significant for female applicants, reducing a strabismic female applicants ability to obtain employment. The presence of strabismus did not appear to influence hiring decisions of male applicants.

Risk of amblyopia recurrence after cessation of treatment.

BACKGROUND Although amblyopia can be successfully treated with patching or atropine, there have been few prospective studies of amblyopia recurrence once treatment is discontinued. METHODS We enrolled 156 children with successfully treated anisometropic or strabismic amblyopia (145 completed follow-up), who were younger than 8 years of age and who received continuous amblyopia treatment for the previous 3 months (prescribed at least 2 hours of daily patching or prescribed at least one drop of atropine per week) and who had improved at least 3 logMAR levels during the period of continuous treatment. Patients were followed off treatment for 52 weeks to assess recurrence of amblyopia, defined as a 2 or more logMAR level reduction of visual acuity from enrollment, confirmed by a second examination. Recurrence was also considered to have occurred if treatment was restarted because of a nonreplicated 2 or more logMAR level reduction of visual acuity. RESULTS Recurrence occurred in 35 (24%) of 145 cases (95% confidence interval 17% to 32%) and was similar in patients who stopped patching (25%) and in patients who stopped atropine (21%). In patients treated with moderately intense patching (6 to 8 hours per day), recurrence was more common (11 of 26; 42%) when treatment was not reduced prior to cessation than when treatment was reduced to 2 hours per day prior to cessation (3 of 22; 14%, odds ratio 4.4, 95% confidence interval 1.0 to 18.7). CONCLUSIONS Approximately one fourth of successfully treated amblyopic children experience a recurrence within the first year off treatment. For patients treated with 6 or more hours of daily patching, our data suggest that the risk of recurrence is greater when patching is stopped abruptly rather than when it is reduced to 2 hours per day prior to cessation. A randomized clinical trial of no weaning versus weaning in successfully-treated amblyopia is warranted to confirm these observational findings.

Therapeutic outcomes of cryotherapy versus transpupillary diode laser photocoagulation for threshold retinopathy of prematurity

INTRODUCTION We undertook this study to compare the clinical outcomes in patients treated for threshold retinopathy of prematurity (ROP) with transpupillary diode laser photocoagulation versus transscleral cryotherapy. METHODS A retrospective chart review was performed of patients treated for threshold ROP at our institution between 1988 and 1997. Cryotherapy was used to treat patients before 1992, and diode laser was used thereafter. One hundred fifteen eyes of 63 patients underwent cryotherapy, and 130 eyes of 70 patients underwent laser treatment. Because strong concordance exists between fellow eyes treated for ROP, statistical analysis was done for right eye outcomes only. Demographics, short-term complications, and treatment parameters were compared on the entire cohort of patients. Structural outcomes were compared between a group of 79 cryotreated eyes (39 OD, 40 OS) and a group of 113 laser-treated eyes (56 OD, 57 OS). Mean cycloplegic refraction was compared between a group of 38 cryotreated eyes (18 OD, 20 OS) and a group of 90 laser-treated eyes (46 OD, 44 OS). Visual acuity for preverbal and nonverbal children was estimated and converted to a Snellen visual acuity equivalent. Geometric mean visual acuity was then compared between a group of 44 cryotreated eyes (22 OD, 22 OS) and a group of 92 laser-treated eyes (47 OD, 45 OS). Patients were included in each outcome analysis if adequate documentation was present in the patient record. RESULTS Demographics and short-term complications were not significantly different between the 2 groups. In the statistical group, 22 of 39 right eyes (56.4%) in the cryotherapy group versus 49 of 56 right eyes (87.5%) in the laser group had resolution of ROP after treatment (P = .0008). Mean spherical equivalent cycloplegic refraction at 12 months of age and over the follow-up period was not significantly different between the cryotherapy and laser groups. Estimated geometric mean visual acuity in the cryotherapy group was 20/103 and in the laser group was 20/49 at 12 months of age (P= .0099). CONCLUSIONS Diode laser photocoagulation was associated with a better long-term structural outcome and visual acuity compared with cryotherapy for the treatment of threshold ROP. Refractive error was not significantly different between the 2 groups over an equivalent follow-up period.

Management and complications of congenital dacryocele with concurrent intranasal mucocele

INTRODUCTION The association of dacryocele and intranasal mucocele has been previously reported. Its incidence and optimal treatment are unknown. PATIENTS AND METHODS A retrospective review of 22 patients with 30 dacryoceles was performed to determine the mean age at presentation, sex distribution, and prevalence of associated intranasal mucocele, associated dacryocystitis, and respiratory distress. The components of the examination, ancillary tests, treatment modalities, and treatment outcomes were then summarized. RESULTS Unilateral dacryoceles were seen in 16 (73%) of the infants, and bilateral dacryoceles were seen in 6 (27%) of the infants. Four (25%) of the 16 patients who initially had unilateral dacryoceles later developed bilateral dacryoceles. Dacryocystitis, preseptal cellulitis, or both were present on presentation or developed in 18 (60%) of 30 dacryoceles. Nasal endoscopy was performed on 13 (59%) of 22 patients. Nasal examination with nasal speculum and headlight was performed on 7 patients (32%). A concurrent intranasal mucocele was diagnosed in 23 (77%) of 30 dacryoceles. Respiratory distress arose in 5 (71%) of 7 patients with bilateral intranasal mucoceles and in 2 (22%) of 9 patients with a unilateral intranasal mucocele. Thirty-four procedures were performed. Seven dacryoceles (21%) were treated with nasolacrimal duct probing under topical anesthesia. Another one (3%) was treated with needle aspiration with later definitive therapy. All other procedures were managed under general anesthesia. These included 2 nasolacrimal duct probings (6%), 2 probings with silicone tube placement (6%), 10 probings with intranasal mucocele marsupialization and silicone tube placement (29%), and 12 probings with marsupialization alone (35%). Two (29%) of the 7 probings performed under topical anesthesia failed, whereas all other procedures were successful. One dacryocele spontaneously resolved. CONCLUSIONS Congenital dacryoceles are commonly associated with intranasal mucoceles, dacryocystitis, and preseptal cellulitis. Respiratory distress is common in bilateral cases. Bilateral nasolacrimal duct probing should be considered in unilateral cases because of the high incidence of occult contralateral involvement.

PHACE: a neurocutaneous syndrome with important ophthalmologic implications: Case report and literature review

OBJECTIVES To introduce PHACE syndrome (Posterior fossa malformations, Hemangiomas, Arterial anomalies, Coarctation of the aorta and other cardiac defects, and Eye abnormalities) to the ophthalmologic literature; to report the first case of PHACE syndrome associated with congenital glaucoma; and to review the ocular and systemic findings that may occur in this entity. DESIGN Case report and literature review. METHODS The authors report a child with PHACE syndrome and congenital glaucoma and review the ophthalmologic and systemic manifestations of this syndrome. RESULTS A 9-month-old girl with PHACE syndrome was treated. She had a large right facial hemangioma, central nervous system (CNS) abnormalities, and cardiac anomalies. Glaucoma was detected in her left eye, and she underwent glaucoma surgery. She did well following two glaucoma procedures, and the facial hemangioma is responding to medical treatment. CONCLUSIONS Ophthalmologists who examine children with large facial hemangiomas should consider PHACE syndrome in the differential diagnosis and should obtain appropriate CNS imaging studies and cardiac evaluation when the diagnosis is suspected. Congenital glaucoma should be added to the list of PHACE-associated ocular anomalies.

Optic neuritis in children: Clinical features and visual outcome☆☆☆

BACKGROUND The purpose of this paper is to study the clinical spectrum of pediatric optic neuritis. We evaluated the presenting features, neuroimaging findings, cerebrospinal fluid abnormalities, associated systemic disease, and visual outcome in patients with this condition. METHODS A retrospective analysis was performed on all patients who came to Baylor College of Medicine with optic neuritis during a 6-year period from 1991 to 1997. The degree of initial visual loss, subsequent visual recovery, and associated disease were reviewed. Magnetic resonance images and cerebrospinal fluid findings were also analyzed. RESULTS Twenty-five patients (39 eyes) 21 months of age to 18 years of age were included in the study, with a mean follow-up of 11 months. Fourteen patients (56%) had bilateral optic neuritis, and 11 patients (44%) had unilateral disease. Thirty-three of 39 eyes (84%) had visual acuity of 20/200 or less at presentation. Twenty-one of 25 patients (84%) were given intravenous methylprednisolone (10 to 30 mg/kg/day). Thirty of 39 eyes (76%) recovered 20/40 visual acuity or better. Three of 39 eyes (7%) recovered vision in the 20/50 to 20/100 range. Six of 39 eyes (15%) recovered vision of 20/200 or less. Twenty-three of 25 patients (92%) underwent magnetic resonance imaging of the brain. A normal magnetic resonance image of the brain was associated with recovery of 20/40 or better visual acuity in 6 of 6 affected eyes (100%). Seven patients were 6 years of age or younger at presentation. Six of 7 (85%) had bilateral disease, and 12 of 13 (92%) affected eyes recovered 20/40 visual acuity or better. Eighteen patients were 7 years of age or older at presentation. Eight of 18 (44%) had bilateral disease, and 10 of 18 patients (56%) had unilateral disease. Eighteen of 26 affected eyes (50%) recovered 20/40 visual acuity or better. CONCLUSION Pediatric optic neuritis is usually associated with visual recovery; however, a significant number (22%) remain visually disabled. A normal magnetic resonance image of the brain may be associated with a better outcome. Younger patients are more likely to have bilateral disease and a better visual prognosis.

Early strabismus surgery for thyroid ophthalmopathy

OBJECTIVE To determine whether strabismus surgery during active thyroid ophthalmopathy is beneficial for selected patients. DESIGN Case series. PARTICIPANTS Eight patients with severe restrictive strabismus due to thyroid ophthalmopathy underwent early strabismus surgery and were followed for a minimum of 16 months after their initial surgery. INTERVENTION All eight patients underwent strabismus surgery while their thyroid ophthalmopathy was evolving. MAIN OUTCOME MEASURES Success was determined by the ability to fuse in the primary position at distance and near without an abnormal head position, and the absence of vision-threatening complications related to strabismus surgery. RESULTS All eight patients achieved successful long-term alignment. Four patients (50%) required more than one operation. CONCLUSIONS Strabismus surgery during active thyroid ophthalmopathy can result in long-term stable alignment and may be a useful alternative in selected patients with marked disability due to thyroid ophthalmopathy.

Use of augmented rectus muscle transposition surgery for complex strabismus

PURPOSE Full tendon rectus muscle transposition surgery augmented with posterior fixation sutures has been shown to be effective in the treatment of abducens palsy and Duanes syndrome. The purpose of this study is to summarize our experience with the use of this procedure and a three fourths partial tendon transposition modification of this procedure for a variety of complex vertical and horizontal paralytic eye movement disorders. DESIGN Retrospective noncomparative interventional consecutive case series. PARTICIPANTS Eighteen patients with paralytic strabismus. INTERVENTION Full tendon rectus muscle transposition procedure augmented with posterior fixation sutures (13 patients) or a three fourths partial tendon transposition augmented with posterior fixation sutures (5 patients). MAIN OUTCOME MEASURES Resolution of diplopia in the primary position and improved ocular alignment. RESULTS Comparing preoperative to postoperative status, presence of primary position diplopia decreased from 64% to 14%, anomalous head posture decreased from 56% to 6%, and primary position alignment improved in all patients. CONCLUSIONS Full tendon rectus muscle transposition surgery augmented with posterior fixation sutures and the vessel-sparing three fourths partial tendon transposition modification of this technique are effective for the treatment of a variety of complex vertical and horizontal paralytic ocular motility disorders.

Association of candidemia and retinopathy of prematurity in very low birthweight infants

OBJECTIVE To determine if the presence of candidemia in infants is associated with an increased incidence of threshold retinopathy of prematurity (ROP). DESIGN Retrospective, case-controlled study. PARTICIPANTS AND CONTROLS Forty-six infants admitted to the Texas Childrens Hospital Neonatal Intensive Care Unit between 1989 and 1999 with a birth weight 1500 g or less, estimated gestational age (EGA) 28 weeks or less, and in whom candidemia developed were matched to a control group of 46 infants based on corresponding birth weight, EGA, and year of birth. METHODS Records of each infant were reviewed to determine the presence and severity of ROP. MAIN OUTCOME MEASURES Development of threshold ROP, including retinal detachment. RESULTS Forty-three infants (93.5%) with candidemia and 39 (84.8%) without candidemia had ROP. Twenty-four infants (52.2%) with candidemia reached threshold and required surgical intervention, compared with 11 infants (23.9%) without candidemia (adjusted odds ratio [OR], 7.4; 95% confidence interval [CI], 1.7-32.1; P = 0.008). Retinal detachment developed in 10 of 24 candidemic infants (41.7%) who reached threshold ROP, compared with 2 of 11 infants (18.2%) without candidemia (OR, 4.4; 95% CI, 0.73-26.9; P = 0.1). CONCLUSIONS Candidemia is associated with increased risk of threshold ROP. Infants with Candida sepsis should be monitored closely for the development of ROP and progression after treatment.