Simon E. Skalicky

Depression and quality of life in patients with glaucoma: a cross-sectional analysis using the Geriatric Depression Scale-15, assessment of function related to vision, and the Glaucoma Quality of Life-15.

PurposeTo determine the prevalence of depression and its association with visual field impairment, quality of life, objective assessment of visual function, and glaucoma severity in elderly patients with glaucoma. DesignCross-sectional study. Participants and ControlsOne hundred sixty-five patients with mild (n=60), moderate (n=43), or severe (n=28) glaucoma and 34 controls with ocular hypertension were enrolled. Severity was stratified according to the Nelson Glaucoma Severity Scale (based on the degree of binocular visual field loss). Groups were substratified according to age. MethodsDemographic information was collected via interviews; the Geriatric Depression Scale-15 and Glaucoma Quality of Life-15 (GQL-15) questionnaires were administered. Visual function was assessed by clinical examination and visual field testing. A subset of patients (n=68) underwent objective assessment of function related to vision. Group differences were evaluated using analysis of variance; Kruskall-Wallis analysis of ranks was performed with significance set at P<0.05. Age-adjustment of P values was performed using analysis of covariance for parametric data and Kruskall-Wallis analysis on age-stratified nonparametric data. A binary univariate regression analysis modeled depression to suspected risk factors. Significant predictive variables were modeled in a multivariate regression analysis. ResultsDepression was more prevalent with increasing glaucoma severity, reaching statistical significance in patients aged 70 to 79 years (P<0.02). Summary and subfactor GQL-15 scores reflected decreased quality of life with increasing glaucoma severity. Assessment of function related to vision scores indicated worsening visual function with increasing glaucoma severity. On multivariate regression analysis, depression status was correlated with age and GQL-15 summary score. ConclusionsDepression is more common in patients with increasing glaucoma severity (age, 70 to 79 y). In patients with glaucoma or ocular hypertension, age and GQL-15 summary score are independent risk factors for depression.

Ocular Surface Disease and Quality of Life in Patients With Glaucoma

PURPOSE To investigate the relationship between ocular surface disease and glaucoma-related quality of life (QoL), glaucoma severity, and treatment in patients with open-angle glaucoma. DESIGN Cross-sectional study. METHODS SETTING Clinical practice. STUDY POPULATION One hundred twenty-four participants-patients with mild (n = 48), moderate (n = 34), or severe (n = 19) glaucoma and 23 controls (glaucoma suspects) not receiving glaucoma treatment-were enrolled. Severity was stratified according to binocular visual field loss. OBSERVED PROCEDURES: Demographic information, the Ocular Surface Disease Index (OSDI), and Glaucoma Quality of Life-15 (GQL-15) questionnaires were administered. MAIN OUTCOME MEASURES OSDI score, GQL-15 score, number and type of glaucoma medications, daily dose of benzalkonium chloride (BAK), and visual field indices. RESULTS OSDI scores and the number of patients with OSD increased with increasing glaucoma severity (P < .001 and P < .005). GQL-15 scores reflected decreased QoL with increasing glaucoma severity (P < .001). These trends were maintained after sub-stratification for age and sex. On univariate regression OSDI was significantly correlated with GQL-15 summary score, glaucoma severity, multiple topical glaucoma medications, worse eye mean deviation and pattern standard deviation, use of topical beta blockers, topical carbonic anhydrase inhibitors, daily dose of BAK, and glaucoma filtration surgery. On multivariate regression GQL-15 summary score (odds ratio [OR] 4.14, 95% confidence interval [CI] 2.59-6.63, P < .001) and a daily dose of BAK greater than 3 (OR 2.47, 95% CI 1.17-5.21, P = .018) were predictive of OSDI score. CONCLUSIONS OSD is more common in patients with increasing glaucoma severity and is associated with poorer glaucoma-related QoL and higher exposure to BAK.

P2Y2 receptor agonists for the treatment of dry eye disease: a review

Recent advances in the understanding of dry eye disease (DED) have revealed previously unexplored targets for drug therapy. One of these drugs is diquafosol, a uridine nucleotide analog that is an agonist of the P2Y2 receptor. Several randomized controlled trials have demonstrated that the application of topical diquafosol significantly improves objective markers of DED such as corneal and conjunctival fluorescein staining and, in some studies, tear film break-up time and Schirmer test scores. However, this has been accompanied by only partial improvement in patient symptoms. Although evidence from the literature is still relatively limited, early studies have suggested that diquafosol has a role in the management of DED. Additional studies would be helpful to delineate how different subgroups of DED respond to diquafosol. The therapeutic combination of diquafosol with other topical agents also warrants further investigation.

Microphthalmia, Anophthalmia, and Coloboma and Associated Ocular and Systemic Features Understanding the Spectrum

IMPORTANCE Microphthalmia, anophthalmia, and coloboma form an interrelated spectrum of congenital eye abnormalities. OBJECTIVE To document the ocular and systemic findings and inheritance patterns in patients with microphthalmia, anophthalmia, and coloboma disease to gain insight into the underlying developmental etiologies. DESIGN, SETTING, AND PARTICIPANTS This retrospective consecutive case series was conducted at a tertiary referral center. Included in the study were 141 patients with microphthalmia, anophthalmia, and coloboma disease without a recognized syndromic etiology who attended the Westmead Childrens Hospital, Sydney, from 1981-2012. EXPOSURE Cases were grouped on the basis of the presence or absence of an optic fissure closure defect (OFCD); those with OFCD were further subdivided into microphthalmic and nonmicrophthalmic cases. Anophthalmic cases were considered as a separate group. MAIN OUTCOMES AND MEASURES Associated ocular and systemic abnormalities and inheritance patterns were assessed. RESULTS Of 141 cases, 61 (43%) were microphthalmic non-OFCD (NOFCD), 34 (24%) microphthalmic OFCD, 32 (23%) nonmicrophthalmic coloboma (OFCD), 9 (6%) anophthalmic, and 5 (4%) were unclassified. Sixty-three (45%) had bilateral disease. Eighty-four patients (60%) had an associated ocular abnormality; of these, cataract (P < .001) and posterior segment anomalies (P < .001) were most common in the NOFCD group. Forty-eight (34%) had an associated systemic abnormality, most commonly neurological, musculoskeletal and facial, urological and genital, or cardiac. Neurological abnormalities were most common in the anophthalmic group (P = .003), while urological abnormalities were particularly seen in the OFCD groups (P = .009). Familial cases were identified in both the OFCD and NOFCD groups, with a likely autosomal dominant inheritance pattern in 9 of 10 families. CONCLUSIONS AND RELEVANCE This series indicated that the OFCD/NOFCD distinction may be useful in guiding evaluation for ocular and systemic associations, as well as the direction and analysis of genetic investigation.

Glaucoma filtration surgery following sustained elevation of intraocular pressure secondary to intravitreal anti-VEGF injections

BACKGROUND AND OBJECTIVE To document cases of sustained elevation of intraocular pressure (IOP) while receiving intravitreal anti-vascular endothelial growth factor (VEGF) agents and subsequent management. PATIENTS AND METHODS A retrospective series of all cases managed by the authors and colleagues was performed. RESULTS Six patients developed sustained elevated IOP; five received ranibizumab and one bevacizumab. Four received unilateral and two received bilateral injections. Two had preexisting primary open-angle glaucoma and one had pseudoexfoliative glaucoma, all with stable IOP prior to anti-VEGF treatment. Angles were open in all cases. Peak IOP averaged 43 mm Hg (range: 34 to 60 mm Hg). The mean number of injections preceding the IOP increase was 10 (range: 1 to 20). Four patients required trabeculectomy, one selective laser trabeculoplasty, and one multiple topical medications. CONCLUSION A sustained increase in IOP requiring glaucoma filtering surgery is a rare but important treatment complication for patients receiving intravitreal anti-VEGF therapy, especially those with preexisting glaucoma or glaucoma risk factors.

Syphilitic uveitis and optic neuritis in Sydney, Australia

Aims To describe ocular syphilis presentations to a tertiary referral eye hospital over a 5-year period and to document HIV coinfection frequency. Methods A retrospective chart review was conducted of consecutive ocular syphilis presentations to Sydney Eye Hospital from 2007 to 2012. Inclusion criteria were positive syphilis serology, ocular inflammation on clinical examination and appropriate syphilis treatment. Outcome measures were clinical features at presentation and best-corrected visual acuity (BCVA) at interval follow-up. Results Thirty-seven eyes of 25 patients were included in the series. Patients were predominantly male (92.0%, p<0.05) with mean age 43.7±14.0 years. Eight (32.0%) patients had confirmed HIV coinfection, three newly diagnosed with HIV. Twelve (32.4%) eyes demonstrated anterior segment involvement with anterior uveitis. Twenty-five (67.6%) eyes demonstrated posterior segment involvement, including panuveitis, acute syphilitic posterior placoid chorioretinitis, retinitis, necrotising retinitis, punctate retinitis and optic neuritis. There was a significant improvement in BCVA for involved eyes (p<0.05) at 1 month and 2–3 months follow-up. Conclusions The clinical findings of 37 eyes with ocular syphilis demonstrated a broad spectrum of clinical manifestations. Rates of HIV coinfection were high, with patients exhibiting both anterior and posterior segment inflammation. Visual outcome improved following syphilis treatment.

Australian Cancer Network Clinical Practice Guidelines for the Management of ocular and periocular Melanoma: an evidence-based literature analysis

Background:  With recent advances in the diagnosis and management of ocular and periocular melanoma, many of which are based on results from randomized control trials, there is an increasing need for an evidence‐based review of the literature for the Australasian population. The Australian Cancer Network has recently redeveloped the evidence‐based Clinical Practice Guidelines for the Management of Melanoma, including a chapter on ocular melanoma. These are the first evidence‐based guidelines on ocular melanoma to be created by the Australian Cancer Network.

Cataract and quality of life in patients with glaucoma

To assess the impact of cataract on quality of life (QoL) for patients with glaucoma.

Benign paroxysmal tonic upgaze of childhood in a hypotonic infant with Beckwith–Wiedemann syndrome

We describe a 9-month-old boy with Beckwith–Wiedemann syndrome (BWS) who developed paroxysmal tonic upgaze (PTU) shortly after birth. His 34-year-old mother with one previously healthy child had no antenatal risk factors or significant family history identified during an uncomplicated pregnancy. A fetal anomaly scan at 19 weeks was unremarkable. The infant was born at 41.5 weeks vaginally with no fetal distress apparent in labour. Weight, length and head circumference were above the 97th percentile. Four hours after birth the infant developed respiratory distress requiring positive pressure ventilation maintaining his oxygen saturations above 85% at all times. Over the following days, he developed features not uncommon in prematurity, including mild hypoglycaemia corrected by dextrose and some polycythaemia which resolved spontaneously. Subsequently, he developed feeding difficulty. Hypotonia with normal power was noted. He developed intermittent episodes of tonic upgaze lasting seconds within 2 weeks of birth. These episodes followed a pattern seen in PTU, occurring irregularly, initially 12–15 times daily while awake. They have gradually abated over 9 months, now only occurring when the infant is fatigued. The episodes of ocular supraversion occurred with neck flexion; however, down-beating nystagmus was not present. His hypotonia has persisted. His dysmorphic features included a prominent left forehead, small ears with no hearing defect, hypertelorism, deepset eyes, a prominent nose, micrognathia and single palmar creases (Fig. 1). He was investigated for an overgrowth syndrome. There was no evidence of maternal diabetes. The child’s insulin-like growth factor-2 (IGF-2) level was elevated. Genetic testing revealed uniparental disomy of 11p15, confirming BWS. Tests for Prader–Willi syndrome, Sotos syndrome, Simpson–Golabi–Behmel syndrome were negative and karyotype was normal. A brain ultrasound and magnetic resonance imaging were within normal limits. Abdominal ultrasound detected splenomegaly but no malignancy. He was reviewed at 3 weeks and 7 months age at the neonatal ophthalmic clinic. At 3 weeks no ocular misalignment or retinopathy was detected. At 7 months his Teller acuity was appropriate at 6/18 with both eyes open, and pupil reactions were normal. Visual fixation was normal without nystagmus and saccadic, pursuit and convergence ocular movements were normal. There was visual fusion deduced from the oculomotor response to a 15-D base-out prism challenge to either eye. Anterior ocular and fundal examination were normal. Paroxysmal tonic upgaze of childhood is a distinctive syndrome of abnormal ocular movement frequently associated with other central nervous features, first observed by Ouvrier and Billson in 1988. The syndrome, with onset usually before 1 year of age, is characterized by brief episodes of sustained ocular supraversion, with compensating neck flexion and frequently down-beating saccades. The symptoms are exacerbated by fatigue and febrile illness and relieved by sleep. Between episodes neurological examination, EEG, imaging and cerebrospinal fluid neurotransmitter studies are typically normal. Associations with ataxia, hypotonia, epilepsy, developmental delay, language disorders, fetal exposure to valproate, periventricular leukomalacia, vein of Galen malformation, hypomyelination and pinealoma have been reported. Autosomal dominant inheritance and abnormal duplicates of chromosome 15 have been described. The pathogenesis of PTU is unknown. It may be a transient developmentally related phenomenon, or part of widespread neurological dysfunction affecting corticomesencephalic control of vertical eye movement. Some authors suggest that the common abnormality is in the periaqueductal grey area. Although the ocular features of PTU generally disappear within a few years, cases not infrequently have persisting ataxia, minor oculomotor disorders and borderline cognitive abilities. Figure 5. Inferotemporal indentation at ora serrata shows reverse horse shoe tear with radial torn edges (verticle black arrows) and a flap directed posteriorly (horizontal black arrow). Letters to the Editor 291

Surgical outcomes of combined trabeculectomy-cyclodialysis for glaucoma.

Purpose:To determine the performance of combined trabeculectomy-cyclodialysis surgery over a 25-year period. Methods:A retrospective cohort study of 55 eyes (39 patients) treated between 1987 and 2012 was performed.The following data were collected: age, sex, glaucoma etiology, preoperative and postoperative number of topical medications, preoperative and postoperative laser trabeculoplasty, intraoperative and postoperative 5-fluorouracil application, lens status at the time of surgery, postoperative cataract surgery, duration of follow-up, and complications. Best-corrected LogMAR visual acuity was assessed preoperatively, at 1 year, and then at 2-yearly intervals for the duration of follow-up. Intraocular pressure (IOP) was assessed preoperatively and then at 1 week, 4 weeks, 1 year, and then at 2-yearly intervals for the duration of follow-up. Visual field indices were collected at baseline and at the completion of follow-up.Failure was defined as reoperation for glaucoma, progression to legal blindness, IOP⩽5 mm Hg, >21 mm Hg, or <20% reduction below baseline. All others were a “complete success” if no additional topical medication was required and a “qualified success” if medication was required. Analyses using 18 and 15 mm Hg as upper limits for success were also performed. Results:Mean IOP fell from 25.2 to 11.9 mm Hg over a mean 11.2 years. At completion of follow-up 32 eyes (58.2%) achieved an unqualified success, 18 (32.7%) a qualified success, and 5 (9.1%) a failure. No patient progressed to legal blindness. Cases with greater preoperative IOP had a greater reduction in IOP (P<0.0001). On univariate analysis no intraoperative application of antimetabolite (OR, 0.74; 95% CI, 0.49-0.94; P=0.022) and a longer follow-up (OR, 1.16; 95% CI, 1.02-1.33; P=0.025) predicted a higher final IOP; these were not significant on multivariate analysis. Thirty-six of 47 phakic eyes developed cataract; the majority occurred in the first 4 years. Conclusion:Combined trabeculectomy-cyclodialysis produces sustained lowering of IOP for long periods of time, despite a cataractogenic effect.