Elizabeth A. Bradley

Paraneoplastic autoimmune optic neuritis with retinitis defined by CRMP-5-IgG

Autoantibodies have defined two paraneoplastic visual disorders related to small‐cell lung carcinoma: retinopathy (“CAR”‐IgG [23kDa, recoverin]) and optic neuritis collapsin response‐mediated protein 5 (CRMP‐5‐IgG [62kDa]). Among 16 patients with CRMP‐5‐IgG and optic neuritis (aged 52–74 years; all smokers, 9 women), we documented coexisting retinitis in 5. None had CAR‐IgG. Fifteen had subacute vision loss, swollen optic discs, and field defects. Vascular leakage was evident at and remote from the disc; 5/5 tested had abnormal electroretinograms. Nine had striking vitreous cells. Vitrectomy showed reactive lymphocytosis (4/4), predominantly CD4+ (1/1). Most patients had multifocal neurological accompaniments. Cerebrospinal fluid contained lymphocytes (7‐32), elevated protein, multiple oligoclonal immunoglobulin bands, and CRMP‐5‐IgG. Three patients superficially resembled Devics disease at presentation. One autopsied patient had predominantly CD8+ T lymphocytes infiltrating optic nerve and spinal cord. Eleven patients had confirmed small‐cell carcinoma; 1 had imaging evidence of lung cancer; 3 had renal or thyroid carcinoma. Full‐length CRMP‐5 protein was identified in normal retina and optic nerve by Western blot analyses. Photoreceptor cells, retinal ganglion cells, and nerve fibers exhibited CRMP‐5–specific immunoreactivity. In summary, CRMP‐5‐IgG defines a paraneoplastic ophthalmological entity of combined optic neuritis and retinitis with vitreous inflammatory cells. Positive serology obviates the need for vitreous biopsy and expedites the search for cancer. Ann Neurol 2003

Development of a Quality-of-Life Questionnaire for Adults with Strabismus

PURPOSE We report the development of a patient-derived, health-related quality-of-life (HRQOL) questionnaire for adults with strabismus. DESIGN Cross-sectional study. PARTICIPANTS Twenty-nine patients with strabismus in a first phase, and 32 patients with strabismus, 18 patients with other eye diseases, and 13 visually normal adults in a second phase. METHODS Individual patient interviews generated 181 questionnaire items. For item reduction, we asked 29 patients with strabismus to complete the 181-item questionnaire, analyzed responses, and performed factor analysis. Two prominent factors were identified, and the 10 items with the highest correlation with each factor were selected. The final 20-item questionnaire (10 psychosocial items and 10 function items) was administered to an additional 32 patients with strabismus (22 with diplopia, 10 without diplopia), 13 visually normal adults, and 18 patients with other eye diseases. A 5-point Likert-type scale was used for responses (never = 100, rarely = 75, sometimes = 50, often = 25, and always = 0). Median overall questionnaire scores and psychosocial and function subscale scores, ranging from 0 (worst HRQOL) to 100 (best HRQOL), were compared across groups. MAIN OUTCOME MEASURES The HRQOL questionnaire response scores. RESULTS Median overall scores were statistically significantly lower (worse quality of life) for patients with strabismus (56) compared with visually normal adults (95; P<0.001) and patients with other eye diseases (86; P<0.001). Median scores on the psychosocial subscale were significantly lower for strabismus patients (69) compared with visually normal adults (99; P<0.001) and patients with other eye diseases (94; P<0.001). For the function subscale, median scores were again significantly lower for strabismus patients (43) compared with visually normal adults (91; P<0.001) and patients with other eye diseases (78; P<0.001). CONCLUSIONS We have developed a 20-item, patient-derived, HRQOL questionnaire specific for adults with strabismus, with subscales to assess psychosocial and function concerns. This 20-item, condition-specific questionnaire will be useful for assessing HRQOL in individual strabismus patients and also as an outcome measure for clinical trials. FINANCIAL DISCLOSURE(S) The authors have no proprietary or commercial interest in any materials discussed in this article.

Development and initial validation of quality of life questionnaires for intermittent exotropia

PURPOSE The development and initial validation of patient-derived, health-related quality-of-life (HRQOL) questionnaires for intermittent exotropia (IXT). DESIGN Cross-sectional study. PARTICIPANTS In a development phase, 27 children (age, 2-17 years) with IXT and 1 of their parents. In an initial validation phase, 33 children with IXT and 49 control children (age, 5-17 years), along with 1 parent for each child. Children in the control group had no strabismus or amblyopia. METHODS Individual patient interviews generated 35 items for child and proxy (parental assessment of childs HRQOL) questionnaires and 46 items for a parent questionnaire. To reduce to a feasible number of items, questionnaires were administered to 5- to 17-year-old children with IXT (n = 15) and parents of 2- to 17-year-old children with IXT (n = 27). Responses were analyzed using standard item reduction methodology. Three final derived IXT questionnaires (IXTQ): child, proxy, and parent (12, 12, and 17 items, respectively) were administered to children with IXT and control children and to parents of IXT and control children. Likert-type scales ranging from never (100, best HRQOL) to almost always (0, worst HRQOL) were used. MAIN OUTCOME MEASURES Median scores for IXT and control groups, compared using Wilcoxon tests. RESULTS Median child scores were significantly lower (worse HRQOL) in the IXT group compared with the control group: 85 (quartiles, 73-92) versus 92 (quartiles, 79-96; P = 0.04). Median proxy IXTQ scores were significantly lower for IXT children than controls: 83 (quartiles, 75-94) versus 98 (quartiles, 92-100; P<0.0001). Median parent IXTQ scores also were significantly lower in the IXT group compared with the control group: 68 (quartiles, 56-79) versus 93 (quartiles, 87-99; P<0.0001). CONCLUSIONS A new 3-part patient-derived HRQOL questionnaire for children with IXT and their parents has been developed and validated, comprising child, proxy, and parent questionnaires. These questionnaires detect reduced HRQOL in children with IXT as reported by the children themselves and perceived by their parents (proxy report). Childhood IXT also seems to affect parent HRQOL. The IXTQ HRQOL questionnaires may prove useful in the clinical assessment of IXT and for clinical trials. FINANCIAL DISCLOSURE(S) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Comparison of Quality-of-Life Instruments in Adults with Strabismus

PURPOSE To compare two health-related quality-of-life (HRQOL) questionnaires in adults with strabismus: the new 20-item Adult Strabismus (AS-20) questionnaire (developed specifically for Adult Strabismus) and the 25-item National Eye Institute Visual Function Questionnaire (VFQ-25). DESIGN Cross-sectional study. METHODS Eighty-four adult patients with strabismus (median age, 53 years; range, 18 to 81 years) completed the AS-20 and VFQ-25 HRQOL questionnaires. Patients were categorized as diplopic (n = 65) or nondiplopic (n = 19). Subnormal HRQOL was defined as less than the fifth percentile for adults with no visual impairment. The proportion of patients below normal was compared overall and by diplopia status. RESULTS Overall, more patients scored below normal with the AS-20 than with the VFQ-25 (90% vs 29%; P < .0001). Nondiplopic patients more often were below normal on the AS-20 psychosocial subscale than on the function subscale (95% vs 42%; P = .002), whereas diplopic patients were more often below normal on the function subscale (85% vs 68%; P = .01). On the psychosocial subscale, more nondiplopic than diplopic patients scored below normal (95% vs 68%; P = .01); on the function subscale, more diplopic than nondiplopic patients scored below normal (85% vs 42%; P = .0005). The VFQ-25 seemed to be insensitive to nondiplopic strabismus: no patients scored below normal on composite score and no more than 11% scored below normal on VFQ-25 subscales. Of diplopic patients, 37% scored below normal on VFQ-25 composite score. No more than 38% scored below normal on VFQ-25 subscales. CONCLUSIONS The new AS-20 seems to be more sensitive than the VFQ-25 for detecting reduced HRQOL in Adult Strabismus, and therefore may be a more useful tool for clinical assessment and clinical trials.

Functional Indications for Upper Eyelid Ptosis and Blepharoplasty Surgery: A Report by the American Academy of Ophthalmology

OBJECTIVE To evaluate the functional indications and outcomes for blepharoplasty and blepharoptosis repair by assessing functional preoperative impairment and surgical results. METHODS Literature searches of the PubMed and Cochrane Library databases were conducted on July 24, 2008, with no age or date restrictions, and they were limited to articles published in English. These searches retrieved 1147 citations; 87 studies were reviewed in full text, and 13 studies met inclusion criteria and were included in the evidence analysis. RESULTS The 13 studies reported the functional effects or treatment results of simulated ptosis; several types of blepharoptosis repair, including conjunctiva-Müllers muscle resection, frontalis suspension, and external levator resection; and upper eyelid blepharoplasty. CONCLUSIONS Repair of blepharoptosis and upper eyelid dermatochalasis provides significant improvement in vision, peripheral vision, and quality of life activities. Preoperative indicators of improvement include margin reflex distance 1 (MRD(1)) of 2 mm or less, superior visual field loss of at least 12 degrees or 24%, down-gaze ptosis impairing reading and other close-work activities, a chin-up backward head tilt due to visual axis obscuration, symptoms of discomfort or eye strain due to droopy lids, central visual interference due to upper eyelid position, and patient self-reported functional impairment. FINANCIAL DISCLOSURE(S) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Surgical correction of blepharoptosis in patients with myasthenia gravis.

PURPOSE To describe the results of surgical correction of blepharoptosis in a series of patients with myasthenia gravis (MG). METHODS In this retrospective case series, we reviewed the medical records of all patients with MG who did not respond to medical therapy and underwent surgical correction for blepharoptosis at the Mayo Clinic between 1985 and 1999. The primary outcome measure was change in interpalpebral eyelid fissure height. RESULTS Sixteen blepharoptosis procedures were performed on 10 patients with MG. Eight of the 10 patients had ocular MG. Two of the 10 patients had systemic MG. Of the 16 procedures performed, 9 were external levator advancements (ELA), six were frontalis slings, and one was a tarsomyectomy. Patients were followed postoperatively for an average of 34 months (range, 14-126 months). The amount of ptosis was quantified pre- and postoperatively for seven of the nine eyelids that underwent ELA. For these seven eyelids (five patients), there was a statistically significant improvement in the mean interpalpebral eyelid fissure height from 3.7 mm preoperatively to 7.8 mm postoperatively, with a mean difference of 4.1 mm (95% confidence interval 1.9 mm to 6.25 mm, p = 0.0038). Postoperative complications included worsened diplopia in one patient with ELA and exposure keratopathy in one patient with frontalis sling. Two of the ELA eyelids developed recurrent ptosis requiring additional surgery more than 2 years after the initial procedure. CONCLUSIONS Blepharoptosis surgery can achieve eyelid elevation in patients who have failed to respond to medical therapy for MG. Potential complications include worsened diplopia and exposure keratopathy.

Ocular manifestations of molluscum contagiosum.

Purpose:  Two cases of molluscum contagiosum (MC) are presented to illustrate the range of potential anterior segment complications of this condition.

Safety and Efficacy of Lacrimal Drainage System Plugs for Dry Eye Syndrome: A Report by the American Academy of Ophthalmology.

OBJECTIVE To review the published literature assessing the efficacy and safety of lacrimal drainage system plug insertion for dry eye in adults. METHODS Literature searches of the PubMed and Cochrane Library databases were last conducted on March 9, 2015, without date restrictions and were limited to English language abstracts. The searches retrieved 309 unique citations. The primary authors reviewed the titles and abstracts. Inclusion criteria specified reports that provided original data on plugs for the treatment of dry eyes in at least 25 patients. Fifty-three studies of potential relevance were assigned to full-text review. The 27 studies that met the inclusion criteria underwent data abstraction by the panels. Abstracted data included study characteristics, patient characteristics, plug type, insertion technique, treatment response, and safety information. All studies were observational and rated by a methodologist as level II or III evidence. RESULTS The plugs included punctal, intracanalicular, and dissolving types. Fifteen studies reported metrics of improvement in dry eye symptoms, ocular-surface status, artificial tear use, contact lens comfort, and tear break-up time. Twenty-five studies included safety data. Plug placement resulted in ≥50% improvement of symptoms, improvement in ocular-surface health, reduction in artificial tear use, and improved contact lens comfort in patients with dry eye. Serious complications from plugs were infrequent. Plug loss was the most commonly reported problem with punctal plugs, occurring on average in 40% of patients. Overall, among all plug types, approximately 9% of patients experienced epiphora and 10% required removal because of irritation from the plugs. Canaliculitis was the most commonly reported problem for intracanalicular plugs and occurred in approximately 8% of patients. Other complications were reported in less than 4% of patients on average and included tearing, discomfort, pyogenic granuloma, and dacryocystitis. CONCLUSIONS On the basis of level II and III evidence in these studies, plugs improve the signs and symptoms of moderate dry eye that are not improved with topical lubrication, and they are well tolerated. There are no level I studies that describe the efficacy or safety of lacrimal drainage system plugs.

Oral Antibiotics for Meibomian Gland-Related Ocular Surface Disease: A Report by the American Academy of Ophthalmology

OBJECTIVE To review the existing medical literature on the role of oral antibiotics in the management of ocular surface disease (OSD) that arises from disorders of the meibomian glands and to assess the efficacy of oral antibiotics in the management of this common ocular disease. METHODS A literature search was last conducted on August 12, 2015, in the PubMed and Cochrane databases for English-language original research investigations that evaluated the role of doxycycline, minocycline, and azithromycin in OSD among adult patients. The searches identified 87 articles, and 8 studies ultimately met the criteria outlined for this assessment. RESULTS The 8 studies identified in the search documented an improvement in meibomian gland-related OSD after treatment with these agents, although side effects were common. This search identified only 1 randomized, controlled trial to assess the efficacy of these medications. CONCLUSIONS Although oral antibiotics are used commonly in the management of OSD, there is no level I evidence to support their use. There are only a few studies that have assessed the efficacy of oral antibiotics in clinically meaningful ways in the management of OSD that arises from disorders of the meibomian glands. The current level of evidence is insufficient to conclude that antibiotics are useful in managing OSD arising from disorders of the meibomian glands. The few existing studies on the topic indicate that oral antibiotics may be an effective treatment for OSD that results from meibomian gland disease.

Radiation-induced meningiomas involving the orbit.

Purpose To review the clinical features and outcomes of patients with radiation-induced meningiomas involving the orbit. Design Retrospective case series. Participants Eight patients with radiation-induced meningiomas affecting the orbit. Methods Clinical and pathologic data of the patients were reviewed. Main Outcome Measures Age at diagnosis, mean interval between radiation therapy and meningioma diagnosis, tumor recurrence, histologic atypia, and mean follow-up time after initial diagnosis. Results The mean age at diagnosis was 42 years (range, 21 years to 70 years). The mean interval between radiation therapy and meningioma diagnosis was 26 years (range, 3 years to 54 years). All patients underwent gross total resection or subtotal resection of the meningioma. Five tumors (62.5%) recurred, based on clinical findings and CT imaging. The mean interval between resection of the meningioma and recurrence was 3 years (range, 9 months to 9 years). Three patients (37.5%) had atypical meningiomas. One patient (12.5%) had multiple tumors. The mean follow-up interval was 7 years after initial diagnosis of the meningioma (range, 15 months to 19 years). Conclusions This series of radiation-induced meningiomas, the first in the ophthalmic literature, illustrates the aggressive nature of this tumor.