Brief Report: Retinal Microvasculature and Immune Restoration Among South Eastern Asian Patients With HIV/AIDS Over a 9-Month Antiretroviral Therapy.

BACKGROUND: Longitudinal evidence on retinal microvasculature and subsequent systemic inflammatory alteration is lacking. We investigated the association between retinal microvasculature and immune response among patients with HIV/AIDS over a 9-month antiretroviral therapy. METHODS: We conducted a prospective cohort study on patients with HIV/AIDS at Singapore Communicable Disease Centre since June 2011. We recruited all eligible patients and then reviewed them every 3 months over a 9-month follow-up, including performing blood tests (CD4+/CD8+ T-cell counts and HIV viral load), blood pressure, anthropometry measurements, and retinal photography at each visit. We assessed retinal vascular indexes using a semiautomated computer-based program. Finally, we applied a linear mixed model to analyze associations between baseline retinal vascular indexes and 9-month changes of CD4+/CD8+ T-cell counts and HIV viral load throughout study observation, after adjusting for major confounders. RESULTS: We found that narrower arteriolar caliber (per 10 µm decrease), wider venular caliber (per 10 µm increase), and larger arteriolar branching angle (per 10° increase) in the retina assessed at baseline were significantly associated with 9-month reductions in CD4+ T-cell count by 52.97 cells/µL (P = 0.006), 33.55 cells/µL (P = 0.01), and 39.09 cells/µL (P = 0.008), accordingly. CONCLUSION: Patients with HIV/AIDS with a suboptimal retinal microvascular morphology tended to fail immune restoration undertaking a 9-month antiretroviral therapy.

Meibomian gland inversion: under-recognized entity.

OBJECTIVE: To describe a clinical entity of upper eyelid margin and meibomian gland inversion (MGI) sequential to meibomian gland dysfunction (MGD), in the absence of eyelash ptosis, trichiasis or manifest marginal entropion. We highlight its clinical features, surgical management and outcomes. METHODS: We performed a retrospective analysis of symptomatic MGI cases refractory to conservative management who underwent surgery in our centre over a 4-year period. Anatomical correction, resolution of symptoms and possible complications are reported. RESULTS: A total of 21 eyelids of 13 patients (mean age: 68.5 ± 15.4, range: 32-88 years) were analysed. Symptomatic MGI patients were operated only if they have noted immediate comfort when we corrected the lid margin position with a cotton tip. Those with refractory superior punctate corneal staining (n = 14 eyes), blink-related discomfort (n = 8) and pseudo-blepharospasm (n = 3) reported complete postoperative resolution. Milder symptoms showed partial improvement: gritty feeling (79%), sore eye (80%) and watery eye (86%). However, symptoms of dry eye disease (DED) persisted in 88% of patients. One case recurred in 6 weeks and was offered revision surgery. Median follow-up was 5 (range: 3-12) months. CONCLUSION: Meibomian gland inversion (MGI) is a subtle clinical entity that can be easily overlooked. Symptoms are often attributed to DED or MGD alone. It is likely that MGI represents early upper lid margin anatomical changes secondary to MGD before cicatricial marginal entropion becomes clinically apparent. Recommended treatment is conservative with intensive lid hygiene and topical MGD management. However, refractory symptomatic cases who respond positively to a 'cotton-tip test' (reversal of lid margin malposition with a rolling cotton-tip) may benefit from surgical intervention with favourable anatomical and functional outcome.

Complications and outcomes of grafting of posterior orbital fat into the lower lid-cheek junction during orbital decompression.

PURPOSE: To report the complications of grafting of excised posterior orbital fat into the lower lid-cheek junction at the time of orbital decompression surgery. METHODS: Retrospective review of consecutive patients undergoing orbital decompression combined with grafting of posterior orbital fat to the pre-malar and lateral canthal area (FG). A second group of consecutive patients undergoing orbital decompression but no orbital fat grafting (NoFG) were also studied as a form of comparative control. Standard patient data, including age, sex, visual acuity, degree of proptosis, operative details, diplopia or any other complications was collected. Independent assessment of pre- and post-operative photographs graded the lower lid-cheek junction. RESULTS: Thirty-four orbits of 29 patients, of which 21 orbits underwent orbital decompression with orbital fat grafting (FG). There were no intraoperative complications, postoperative infections, or visual loss. Complications relating to fat grafting included prolonged swelling in 3 (17%) patients at 3 months, in 1 case lasting 6 months, lower lid lumps in 3 (17%), and fat seepage in 1 (6%). The FG group achieved a greater improvement in the appearance of the lower-lid-cheek junction at 12 months in comparison to NoFG. Mean grade improvement 1.24 ± 1.09 vs 0 ± 0.82 (p = 0.025). Median follow-up was 20 months (range 6-30 months). CONCLUSION: Grafting of excised orbital fat during orbital decompression can improve the appearance of the lower lid-cheek junction in patients being treated for thyroid orbitopathy. However, 24% of patients will experience swelling and/or lumpiness requiring several months to settle or further fat excision.

Late outcomes of gold weights and platinum chains for upper eyelid loading.

AIM: To identify late outcomes of gold weights (GWs) and platinum chains (PCs) for upper eyelid loading in the management of lagophthalmos. METHODS: A retrospective case series of upper eyelid GWs and PCs at a single centre over a 10-year period (2004-2013). Two independent, blinded assessors graded standard photographs for any weight-related morbidity (poor upper eyelid contour, weight prominence and migration). RESULTS: Primary upper eyelid loading (high-tarsal technique) was performed in 154 eyelids of 136 patients (facial nerve palsy, n=99; non-paralytic, n=37). A total of 127 eyelids of 110 patients had primary GW insertion. Of these, 40.9% (52/127) had revision surgery: exchange of GW for PC (58%), GW repositioning (25%) and removal of GW (17%). Only 22.2% (6/27 eyelids) with primary PCs required revision surgery. In those not requiring revision surgery, photograph grading showed that both GWs and PCs had weight-related morbidity at late follow-up (median=37.5 months, range 12-110 vs median=33.5 month, range 15-106). GWs had significantly higher rate of weight prominence (p=0.001) and migration (p<0.001) compared with PCs. All PC revisions required one procedure only compared with 10% of GWs revisions requiring two or more procedures. Incidence of gold allergy was 7% (8/110 patients). There was no association between the choice of weight material, physical weight or suture material and eyelid morbidities. CONCLUSION: GWs were found to be associated with higher complications and twice more likely to require long-term revision surgery compared with PCs. Despite weight fixation at a high-tarsal location, prominence of PCs can still occur.

Non-aesthetic indications for periocular hyaluronic acid filler treatment: a review.

Dermal fillers have been in use for many years for aesthetic rejuvenation of the face. More recently, however, fillers have been increasingly used as an alternative to traditional surgical procedures for non-aesthetic indications. These indications include lagophthalmos, eyelid malpositions and orbital volume deficiency. The advantages of these filler injections are multiple: minimally invasive, repeatable, titratable and even reversible (depending on the product used). We review the current literature of functional uses of filler injections as mentioned above and evaluate the safety profile and efficacy of filler injections for this purpose.

Dataset of longitudinal analysis of tear cytokine levels, CD4, CD8 counts and HIV viral load in dry eye patients with HIV infection.

The data presented in this article shows the longitudinal analysis of tear fluid cytokine profiles, blood CD4 and CD8 counts and HIV viral load in 34 dry eye patients with HIV infection during the HAART therapy. Clinical samples were collected from HIV patients with dry eye disease at the time of presentation to the clinic (visit 1), three months (visit 2) and 6 months (visit 3) after the presentation. At each time point tear samples were evaluated for 41 cytokines using Luminex bead based multiplex assay and blood samples were tested for HIV viral load and CD4 and CD8 counts.

Dataset of tear film cytokine levels in dry eye disease (DED) patients with and without HIV infection.

The tear film cytokine profiling data in this article was obtained from a prospective case-control study with a sample size of 34 dry eye disease (DED) patients with HIV infection and 32 DED patients without HIV infection, see "A distinct cytokines profile in tear film of dry eye disease (DED) patients with HIV infection" (R. Agrawal, P.K. Balne, A. Veerappan, V.B. Au, B. Lee, E. Loo, A. Ghosh, L. Tong, S.C. Teoh, J. Connolly, P. Tan, 2016) [1]. Tear samples were collected from all the subjects using Schirmer׳s strips and cytokine profiling was done using the Luminex bead based multiplex assay with a panel of 41 analytes. The cytokine level differences in each group of subjects were analyzed using logistic regression models.

Validation of CADS Grading Scale: An Ophthalmic Specific Grading Instrument for Facial Nerve Palsy.

PURPOSE: To evaluate the inter- and intraobserver reliability of the CADS score, a previously described facial nerve grading instrument for ophthalmic grading of facial nerve palsy. METHODS: This is a cross-sectional validation study. Two clinicians independently assessed and graded each patient on the same day, masked to each other's grading. Four parameters are assessed in the CADS scale: Cornea (0-3, ±a), static Asymmetry (0-2), Dynamic function (0-3), and Synkinesis (0-2). One clinician reassessed the patients and performed the grading again at a minimum time interval of 1 hour later. A weighted κ analysis was performed to determine inter- and intraobserver reliability using 95% bootstrapped bias-corrected and accelerated (BCa) confidence intervals (CIs). RESULTS: Thirty-three patients (27 women, mean age 51.7, range 23-80 years) with unilateral facial nerve palsy were graded. The overall interobserver reliability was 0.80 (95% BCa CI: 0.68-0.91) for cornea, 0.93 for resting asymmetry (95% BCa CI: 0.55-1.00), 0.80 for dynamic function (95% BCa CI: 0.50-0.96), and 0.88 (95% BCa CI: 0.71-0.96) for synkinesis. The overall intraobserver reliability was 0.93 for cornea (95% BCa CI: 0.83-0.98), 0.82 for resting asymmetry (95% BCa CI: 0.53-0.96), 0.92 for dynamic function (95% BCa CI: 0.72-1.00), and 0.98 for synkinesis (95% BCa CI: 0.84-1.00). CONCLUSION: The CADS grading scale demonstrates good interobserver reliability and very good intraobserver reliability. It incorporates all ophthalmic complications for facial nerve palsy and remains easy to use and refer to.

A distinct cytokines profile in tear film of dry eye disease (DED) patients with HIV infection.

PURPOSE: To investigate the tear cytokine profile in HIV patients with dry eye disease (DED) and study the association between the severity of ocular inflammatory complications and tear cytokines levels. We postulate that HIV-mediated inflammation may be the underlying pathogenic mechanism for HIV-associated DED. METHODS: The current prospective case-control study compared tear film cytokine profiles in DED patients with HIV infection (n=34) and age/gender-matched DED patients without HIV infection [controls (n=32)]. Participants were recruited from tertiary referral eye care centre and communicable disease clinics, Singapore. Ocular surface health was documented using tear film, Schirmer's test, corneal staining, and conjunctival injection measurements. Tear samples were collected using Schirmer's strips and analysed for the levels of 41 cytokines using Luminex bead assay. Logistic regression models were performed to determine correlation and significance. RESULTS: Among the 41 cytokines analysed, statistically significant differences were observed in the mean values of epithelial growth factor (EGF), growth related oncogene (GRO) and interferon gamma-induced protein 10 (IP-10). EGF and IP-10 levels were higher and GRO levels were lower in the tears of DED patients with HIV infection compared to DED patients without HIV infection. No significant association was found between varying levels of ocular surface parameters and cytokine concentrations in HIV patients with DED (p>0.05). CONCLUSIONS: EGF and IP-10 were significantly elevated and GRO levels were lower in the tear profile of HIV patients with DED compared to immunocompetent patients with DED. This study suggests a novel cytokine driven paradigm for ocular inflammatory complications of HIV infection. Additional studies in large organised cohorts can validate the results.

Oculoplastic considerations in patients with glaucoma.

The incidence of glaucoma worldwide is increasing. Often, these patients may also be referred to oculoplastic surgeons for either age-related problems or issues secondary to medical or surgical glaucoma treatment. Eyelid malpositions (ptosis or lid retraction) may occur after glaucoma filtration surgery or the use of prostaglandin analogues. We review the incidence and mechanisms of lid malpositions found in the literature. Surgical correction for these malpositions also requires careful consideration and should be tailored to the individual patient to avoid undesirable surgical outcomes. For instance, overcorrection of ptosis may result in bleb exposure and the risk of blebitis or endophthalmitis. As use of topical prostaglandin analogues increases, we summarize the reports of prostaglandin analogue-associated periocular changes and its underlying etiologic mechanisms. Cessation of these medications may be required in some patients. Where topical treatment is to be continued, eyelid surgery has to be individualized and approached conservatively. It is imperative that patients with glaucoma and oculoplastic concerns be considered as a distinct entity to avoid unfavorable outcomes.

A prospective case-control study to investigate retinal microvascular changes in acute dengue infection.

Dengue infection can affect the microcirculation by direct viral infection or activation of inflammation. We aimed to determine whether measured retinal vascular parameters were associated with acute dengue infection. Patients with acute dengue were recruited from Communicable Diseases Center, Singapore and age-gender-ethnicity matched healthy controls were selected from a population-based study. Retinal photographs were taken on recruitment and convalescence. A spectrum of quantitative retinal microvascular parameters (retinal vascular caliber, fractal dimension, tortuosity and branching angle) was measured using a semi-automated computer-based program. (Singapore I Vessel Assessment, version 3.0). We included 62 dengue patients and 127 controls. Dengue cases were more likely to have wider retinal arteriolar and venular calibers (158.3 µm vs 144.3 µm, p < 0.001; 227.7 µm vs 212.8 µm, p < 0.001; respectively), higher arteriolar and venular fractal dimensions (1.271 vs 1.249, p = 0.002; 1.268 vs. 1.230, p < 0.001, respectively), higher arteriolar and venular tortuosity (0.730 vs 0.546 [x10(4)], p < 0.001; 0.849 vs 0.658 [x10(4)], p < 0.001; respectively), compared to controls. Resolution of acute dengue coincided with decrease in retinal vascular calibers and venular fractal dimension. Dengue patients have altered microvascular network in the retina; these changes may reflect pathophysiological processes in the immune system.

Evaluation of the use of a nurse-administered telephone questionnaire for post-operative cataract surgery review.

PURPOSE: The purpose of this paper is to determine the safety of substituting the first day post-operative review after routine cataract surgery (phacoemulsification) with a telephone survey. DESIGN/METHODOLOGY/APPROACH: Prospective non-randomised cohort study. A standardised questionnaire of five common ocular symptoms (general condition, vision, eye pain, headache, nausea or vomiting) was administered by a trained nurse on the first post-operative day. The patients were reviewed in clinic two to 14 days later. Patient charts were retrospectively reviewed for complications (endophthalmitis, raised intra-ocular pressure, wound leaks and uveitis) requiring deviation from standard treatment. FINDINGS: Over 13 months, 256 eyes of 238 patients underwent uncomplicated phacoemulsification by four consultant surgeons. Only one patient reported poor general condition, blurred vision and eye pain. She was subsequently found to have corneal oedema and raised intra-ocular pressure when recalled for an earlier review. Best corrected visual acuity better than 20/40 was achieved in 80.5 per cent of patients. There were no other post-operative complications noted from medical records review. RESEARCH LIMITATIONS/IMPLICATIONS: Non-randomised nature, skewed surgical expertise, lack of a control group and patient experience data. In all, 22 patients (9.2 per cent) were also uncontactable for the telephone interview. PRACTICAL IMPLICATIONS: A nurse-administered telephone survey seemed to be a safe and effective alternative to first day post-operative review after routine phacoemulsification. The survey also enabled the detection of serious post-operative complications. The first day post-operative hospital visit may be safely substituted in a selected patient population with greater patient convenience achieved and liberation of clinic resources. ORIGINALITY/VALUE: This is the first study which utilises a standardised questionnaire as a form of post-operative review in an Asian population.

Retinal vascular parameter variations in patients with human immunodeficiency virus.

PURPOSE: To compare the retinal vascular parameters in patients with human immunodeficiency virus (HIV) infection with normal controls, and to determine the relationship between retinal vascular parameters and HIV-related blood biomarkers (CD4(+) T-lymphocytes count, presence of HIV RNA). METHODS: Case-control study of eighty-five patients with HIV on follow-up at the Communicable Disease Center, Singapore, and 251 age-, sex-, and race-matched normal healthy controls (case: control matching ≈ 1:3) selected from the Singapore Epidemiology of Eye Disease program were included in this study. Standardized retinal photographs were taken from patients and controls. Trained technicians measured quantitative retinal vascular parameters (retinal vascular caliber, branching angle, tortuosity, and fractal dimension) with a semiautomated computer-based program following a standardized protocol. RESULTS: HIV-patients had more tortuous arterioles (0.77 × [10(4)] vs. 0.59 × [10(4)], P < 0.001) and venules (0.90 × [10(4)] vs. 0.74 × [10(4)], P < 0.001), compared with healthy normal subjects. Amongst the HIV-patients, increasing HIV viral loads were associated with decreased retinal arteriolar caliber (P trend = 0.009) and decreased arteriolar-venular ratio (P trend = 0.025). CONCLUSIONS: Our study showed that patients with HIV have significant variations in retinal vasculature. Retinal vascular imaging may offer further insight into the pathophysiology behind HIV-related vascular disease in future.

Severe optic neuritis in a patient with combined neuromyelitis optica spectrum disease and primary Sjögren's syndrome: a case report.

INTRODUCTION: Optic neuritis, although uncommon, can be the initial presentation of Sjögren's syndrome. Coexisting Sjögren's syndrome has also been reported with neuromyelitis optica spectrum disorder. This case report highlights the association between the two diseases and the importance of rheumatological and neurological evaluations in patients with such diagnoses. Distinction of neuromyelitis optica with coexisting connective tissue disease has both prognostic and therapeutic significance for the patient. CASE PRESENTATION: We report a case of a 56-year-old Chinese woman who presented with bilateral asymmetric visual loss secondary to optic neuritis. She was subsequently found to be seropositive for neuromyelitis optica immunoglobulin G (NMO-IgG) (anti-aquaporin-4 antibody) and was diagnosed with neuromyelitis optica spectrum disorder. She also fulfilled the international criteria for Sjögren's syndrome. Despite initial high dose immunosuppressive therapy, she failed to regain vision in one eye. CONCLUSION: Patients presenting with optic neuritis and severe visual loss should be screened for neuromyelitis optica and treated appropriately. Neuromyelitis optica has been associated with systemic autoimmune diseases, in particular Sjögren's syndrome, and current evidence indicates that they are two distinct entities. We recommend that both diagnoses be considered in cases of optic neuritis with severe visual loss.

Evaluation of the impact of uveitis on visual-related quality of life.

PURPOSE: To determine quality of life in patients with uveitis and investigate the association between clinical parameters of uveitis and visual functioning. METHODS: Prospective cross-sectional study. The interviewer- administered National Eye Institute visual function questionnaire (VFQ-25) was used in 117 adult outpatient uveitic patients. Their scores were compared against 48 controls with no ocular history. Subgroup differences amongst the patients were compared using Mann-Whitney and Kruskal-Wallis test. Multiple regression analysis was performed to determine the associations of visual function and disease characteristics of uveitis. RESULTS: VFQ-25 composite scores for patients were significantly lower than controls in all domains except driving. In multivariable analysis, lower VFQ-25 composite scores were associated with a chronic course of disease, even after taking into account the influences of visual acuity, treatment regimes and location of disease. CONCLUSIONS: Uveitic patients reported poorer visual functioning. A chronic course of disease is associated with poorer functioning.

Simple antenatal preparation to improve breastfeeding practice: a randomized controlled trial.

OBJECTIVE: To address the impact of simple antenatal educational interventions on breastfeeding practice. METHODS: A randomized controlled trial was carried out in a tertiary referral center from May 2002 to December 2004. A random sample of eligible low-risk antenatal patients was recruited from clinics in the National University Hospital, Singapore. Group A received breastfeeding educational material and individual coaching from a lactation counselor. Group B received breastfeeding educational material with no counseling. Group C received routine antenatal care only. RESULTS: A total of 401 women were recruited. Mothers receiving individual counseling and educational material practiced exclusive and predominant breastfeeding more often than mothers receiving routine care alone at 3 months (odds ratio [OR] 2.6, 95% confidence interval [CI] 1.2-5.4) and 6 months (OR 2.4, 95% CI 1.0-5.7) postpartum. More mothers practiced exclusive and predominant breastfeeding at 6 months among women receiving individual counseling compared with women exposed to educational material alone (OR 2.5, 95% CI 1.0-6.3). CONCLUSION: Where breastfeeding practices are suboptimal, simple one-encounter antenatal education and counseling significantly improve breastfeeding practice up to 3 months after delivery. Provision of printed or audiovisual educational material is not enough. Health care workers should make every effort to have one face-to-face encounter to discuss breastfeeding with expectant mothers before they deliver. CLINICAL TRIAL REGISTRATION: (www.ClinicalTrials.gov), NCT002770192 LEVEL OF EVIDENCE: I.