Effective delivery of drugs to the anterior segment of the eye is notoriously inefficient due to the anatomical barriers in place. Topical administration is the most common method of drug delivery to the anterior segment. When applied to the ocular surface, topical solutions encounter barriers such as lacrimal drainage, rapid tear turnover, and reflex blinking which result in < 5% of instilled therapeutic reaching the intended tissue. One potential method to evade some of these anatomical barriers and improve the delivery of therapeutics is the use of mucoadhesive nanoparticles. These materials are designed to encapsulate a relevant ocular therapeutic and provide a means of maintaining the vehicle on the ocular surface by adhering to the mucin layer of the tear film. To this end, the work presented herein describes the design, characterization, and testing of a novel mucoadhesive polymeric nano-micelle ocular drug delivery system. The base polymer used was selected from a system that has been previously used in the Sheardown Lab. It was composed of poly(D,L-lactide)-block-poly(methacrylic acid-co-3-(acrylamido)phenylboronic acid) (PLA-b-P(MAA-co-3-AAPBA); LMP-20). The formulation was modified to replace the 3-AAPBA monomer, which contains phenyl boronic acid as the mucoadhesive component, with a preactivated thiol monomer (pyridyl disulfide ethyl methacrylate; PDSMA) to generate a novel polymer (LMS-20) to investigate the potential for drug incorporation and mucoadhesion. Modifications of the polymer were made with small thiol molecules cysteamine (Cys; LMC-20), glutathione (GSH; LMG-20), and N-acetyl cysteine (NAC; LMA-20) with a goal of reducing cytotoxicity associated with the 2-pyridinethione leaving group. Synthesis of the PDSMA monomer, LMS-20 and LMP-20 polymers, and modified polymers LMC-20, LMG-20, and LMA-20 were confirmed by 1H NMR. LMA-20 was chosen for further examination as it contained the most relevant thiol modification for ocular applications and was capable of nanoprecipitation to form aqueous micelles with previously developed methods. Micelles were formed from LMA-20 and LMP-20, with spherical morphology as confirmed by TEM. Effective diameters of 64 ± 5 nm and 72 ± 3 nm are reported for LMA-20 and LMP-20, respectively, as confirmed by DLS. Critical micelle concentration for LMA-20 of 217 mg/L was found via a pyrene fluorescence study, significantly lower than the concentration of intended application. LMA-20 and LMP-20 are predicted to be mucoadhesive based on results of zeta-potential studies. However, oscillatory rheology studies were inconclusive based on a negative rheological synergism. LMA-20 micelles loaded with 0.16% (w/w) Cyclosporine-A were able to provide sustained release of drug up to 3 days in vitro. These results suggest the possible future use of these preactivated thiomer-based materials for the delivery of therapeutics to the anterior segment. / Thesis / Master of Applied Science (MASc)

No / PURPOSE. Amblyopia is a developmental disorder of spatial vision. There is evidence to suggest that some amblyopes misperceive spatial structure when viewing with the affected eye. However, there are few examples of these perceptual errors in the literature. This study was an investigation of the prevalence and nature of misperceptions in human amblyopia. METHODS. Thirty amblyopes with strabismus and/or anisometropia participated in the study. Subjects viewed sinusoidal gratings of various spatial frequencies, orientations, and contrasts. After interocular comparison, subjects sketched the subjective appearance of those stimuli that had nonveridical appearances. RESULTS. Nonveridical visual perception was revealed in 20 amblyopes (~67%). In some subjects, misperceptions were present despite the absence of a deficit in contrast sensitivity. The presence of distortions was not simply linked to the depth of amblyopia, and anisometropes were affected as well as those with strabismus. In most cases, these spatial distortions arose at spatial frequencies far below the contrast detection acuity cutoff. Errors in perception became more severe at higher spatial frequencies, with low spatial frequencies being mostly perceived veridically. The prevalence and severity of misperceptions were frequently found to depend on the orientation of the grating used in the test, with horizontal orientations typically less affected than other orientations. Contrast had a much smaller effect on misperceptions, although there were cases in which severity was greater at higher contrasts. CONCLUSIONS. Many types of misperceptions documented in the present study have appeared in previous investigations. This suggests that the wide range of distortions previously reported reflect genuine intersubject differences. It is proposed that nonveridical perception in human amblyopia has its origins in errors in the neural coding of orientation in primary visual cortex.

O tratamento cirúrgico da blefaroptose congênita é controverso e, embora a ressecção supramáxima do levantador palpebral tenha sido advogada por alguns autores como eficaz em diminuir a assimetria palpebral, existe o risco de que a cirurgia possa estar associada à restrição dos movimentos palpebrais e à ocorrência de olho seco. Com o objetivo de quantificar os movimentos palpebrais nos pacientes submetidos à cirurgia e avaliar a eventual relação entre supostas alterações funcionais dos movimentos palpebrais e a ocorrência de complicações relacionadas à superfície ocular, foram caracterizadas, mediante a utilização da técnica magnetic search coil, as amplitudes e as velocidades dos movimentos do piscar e dos sacádicos palpebrais dos olhos operados de dezoito pacientes e, em seguida, foram comparadas com as amplitudes e velocidades obtidas para os olhos contralaterais não operados dos mesmos pacientes e também com as obtidas para os olhos dos pacientes do grupo controle, não operados. Também foram avaliados os resultados cosméticos nos pacientes operados e a ocorrência de complicações relacionadas à superfície ocular entre os olhos operados e os controles, não operados. A cirurgia acarretou aumento da distância margem-reflexo da pálpebra superior e diminuição da assimetria palpebral, logrando bom resultado estético. Porém, tanto a amplitude quanto a velocidade, seja das piscadelas, ou dos movimentos sacádicos palpebrais dos olhos operados, foram inferiores às dos controles e a cirurgia esteve relacionada com maior risco de ocorrência de olho seco. Por esse motivo, os autores advogam que a ressecção supramáxima do levantador da pálpebra superior permanece uma opção eficaz para o tratamento da ptose palpebral congênita, mas contraindicam a sua utilização em pacientes com ausência do reflexo de Bell ou outras alterações prévias documentadas ou predisponentes à ceratoconjuntivite seca. / Surgical treatment of congenital blepharoptosis remains controversial and, although supramaximal resection of the levator palpebrae superioris has been advocated as effective in reducing eyelid asymmetry, there is a risk that the surgery may be associated with restriction of eyelid movements and the occurrence of dry eye. In order to quantify eyelid movements in patients undergoing surgery and to assess the possible relationship between the alleged functional changes of eyelid movements and the occurrence of complications related to the ocular surface, we measured by magnetic search coil technique the amplitude and the maximal descent speed of blinks and lid saccades in eighteen patients who undergone surgery and in ten patients of the control group, with no eyelid diseases. We compared the amplitude and speed of the operated eyes with that of the non-operated eyes. We also evaluate the cosmetic results in operated patients and the occurrence of dry eye between operated and non-operated eyes. The surgery resulted in increased upper lid margin-reflex distance and consequent decreased eyelid asymmetry, achieving good aesthetic result. However, both amplitude and speed of eyelid movements in operated eyes were lower than those for the control eyes and the surgery was associated with increased risk of dry eye. For this reason, the authors advocate that supramaximal levator resection of the levator palpebrae superioris remains an effective option for the treatment of congenital blepharoptosis, but contraindicate its use in patients with absence of Bell\'s reflex or with previous ocular surface diseases.

Aim: To assess the ability of critical flicker frequency (CFF) and optimal reading speed (ORS) to predict the potential vision in patients with cataract with and without ocular comorbidity. Methods: The two novel tests were compared with two well established potential vision tests (PVTs), the potential acuity meter (PAM) and the laser interferometer (LI). Measurements were made preoperatively in 1 eye of 88 subjects using the battery of 4 PVTs. Postoperative measurements were made with the CFF and the ORS. The subjects studied were consecutive cases over a 12-month period who fulfilled the inclusion and exclusion criteria, and agreed to participate in this study. Results: CFF was the PVT most resistant to the presence of cataract. Both CFF and ORS give a similar predictive precision in the presence of cataract and ocular comorbidity, although CFF seems more precise when the cataract is dense. Conclusions: The PAM and the LI showed a limited clinical capability in predicting postoperative visual acuity, particularly with dense opacities. The CFF shows the most promise as a PVT, particularly with dense cataract. Further evaluation is required for both CFF and ORS.

Assessment and diagnosis of dry eye disease (DED) is a challenging task. The conventional ways of diagnosing DED are problematic due to their invasiveness, poor test reliability and significant test duration. Previously, ocular surface thermography has been shown to be able to detect early inflammation and dry eye. However, its diagnostic ability and ocular temperature metrics that can best diagnose DED are not clear. The objectives of this thesis were manyfold. First, the prevalence of dry eye in Singapore population was investigated as a helpful basis for the rest of the project. A cross-sectional dry eye survey was carried out using McMonnies dry eye questionnaire. Members of the public were interviewed at 46 (out of 62) selected mass rapid transit stations in Singapore and its vicinity. 1004 questionnaires were collected from participants aged 15 - 83 years and various ethnicity. Prevalence of symptomatic dry eye (SDE) was found to be 12.3% (about 0.5 million Singaporeans). Risk factors associated with SDE were found to be age, gender, ethnicity, hypertension and contact lens wear. Smoking was not associated with SDE.The main part of this thesis sought to evaluate the efficacy of ocular thermography in diagnosing DED. A new infrared detector (NEC Thermo Tracer TH 9260) with relatively high resolution was used. Inter-image, inter-occasion and inter-examiner repeatability was first studied on 21 healthy and 15 DED subjects. Ocular surface marking and ocular surface temperature (OST) acquisition was performed with a novel 'diamond' method using a custom-designed OST analysis V2 software. Ten out of the twelve tested OST indices were shown to be highly repeatable for three studied time points: 0 s, 5 s and 10 s. They were temperatures of the geometric center of the cornea (GCC), mean temperature (MOST) of the region of interest (ROI), maximum (MaxT) and minimum (MinT) temperatures of the ROI, extreme temporal (T1) and nasal conjunctiva (T4), mid temporal (CT) and nasal conjunctiva (CN) and temporal (LT) and nasal limbal (LN). Another 62 DED and 63 age- and sex-matched controls were then recruited and the ten static and dynamic OST indices were evaluated. Static measures were study of absolute OST at t = 0 s, 5 s and 10 s after eye opening. Dynamic measures were study of mean change and net change in OST over 10 s of sustained eye opening. Static measures on eight OST indices (GCC, MOST, MinT, MaxT, T4, CT, LT and LN) at t = 0 s, 5 s and 10 s and dynamic measures on two OST indices (T4 at 3 s onward and MaxT at 5 s onward) were found to be valuable in detecting DED. The temperature metrics (static and dynamic) were identified for further investigation. Thereafter, the diagnostic ability of the temperature metrics were evaluated singly and as combinations in terms of their area under the curve (AUC), Youden index and discrimination power. Receiver operating characteristic curves were plotted for each metric. Best detectors for DED were found to be the T4 temperature metrics: particularly T4-5 and T4-10 (i.e. absolute temperature of the extreme nasal conjunctiva at 5 s and 10 s). Values of T4-5 of < 34.8 °C were found to give sensitivity and specificity of 87.1% and 50.8% respectively and values of T4-10 of < 34.6 °C were found to give sensitivity and specificity of 77.6% and 61.9% respectively. The two temperature metrics had highest Youden index as compared to other metrics and were shown to be useful in view of AUC > 70% but of limited performance in view of their discrimination power. Nevertheless, measuring T4-5 and T4-10 was found to be comparable to other conventional methods for DED. T4-10 was better than T4-5 in view of higher AUC and Youden index. None of the tested dynamic metrics was good detector for DED and combining metrics were not able to increase the diagnostic ability. The last part of this thesis was to validate the effectiveness of some common conventional dry eye tests, to study their correlation with T4 temperature metrics and derive the best composite/combined tests for DED. Sixty two DED patients and 82 controls were studied. The conventional clinical tests examined were: symptom evaluation using McMonnies dry eye questionnaire (Mscore) and symptom count (Scount), fluorescein break-up time (FBUT) and corneal epithelial staining (CES), non-invasive break-up time (NIBUT) and tear meniscus height (TMH). Mscore and Scount was the best detectors for DED, followed by FBUT and CES. Discordance between signs and symptoms for DED was further confirmed. Combining CES with T4-10 (series) can be future objective tests for DED. Further research is warranted, particularly to (1) validate the ability of T4-10 as a stand-alone test for DED and (2) work out an algorithm and validate the diagnostic ability of the recommended combined test (CES and T4-10) using newly recruited subjects.

O tratamento cirúrgico da blefaroptose congênita é controverso e, embora a ressecção supramáxima do levantador palpebral tenha sido advogada por alguns autores como eficaz em diminuir a assimetria palpebral, existe o risco de que a cirurgia possa estar associada à restrição dos movimentos palpebrais e à ocorrência de olho seco. Com o objetivo de quantificar os movimentos palpebrais nos pacientes submetidos à cirurgia e avaliar a eventual relação entre supostas alterações funcionais dos movimentos palpebrais e a ocorrência de complicações relacionadas à superfície ocular, foram caracterizadas, mediante a utilização da técnica magnetic search coil, as amplitudes e as velocidades dos movimentos do piscar e dos sacádicos palpebrais dos olhos operados de dezoito pacientes e, em seguida, foram comparadas com as amplitudes e velocidades obtidas para os olhos contralaterais não operados dos mesmos pacientes e também com as obtidas para os olhos dos pacientes do grupo controle, não operados. Também foram avaliados os resultados cosméticos nos pacientes operados e a ocorrência de complicações relacionadas à superfície ocular entre os olhos operados e os controles, não operados. A cirurgia acarretou aumento da distância margem-reflexo da pálpebra superior e diminuição da assimetria palpebral, logrando bom resultado estético. Porém, tanto a amplitude quanto a velocidade, seja das piscadelas, ou dos movimentos sacádicos palpebrais dos olhos operados, foram inferiores às dos controles e a cirurgia esteve relacionada com maior risco de ocorrência de olho seco. Por esse motivo, os autores advogam que a ressecção supramáxima do levantador da pálpebra superior permanece uma opção eficaz para o tratamento da ptose palpebral congênita, mas contraindicam a sua utilização em pacientes com ausência do reflexo de Bell ou outras alterações prévias documentadas ou predisponentes à ceratoconjuntivite seca. / Surgical treatment of congenital blepharoptosis remains controversial and, although supramaximal resection of the levator palpebrae superioris has been advocated as effective in reducing eyelid asymmetry, there is a risk that the surgery may be associated with restriction of eyelid movements and the occurrence of dry eye. In order to quantify eyelid movements in patients undergoing surgery and to assess the possible relationship between the alleged functional changes of eyelid movements and the occurrence of complications related to the ocular surface, we measured by magnetic search coil technique the amplitude and the maximal descent speed of blinks and lid saccades in eighteen patients who undergone surgery and in ten patients of the control group, with no eyelid diseases. We compared the amplitude and speed of the operated eyes with that of the non-operated eyes. We also evaluate the cosmetic results in operated patients and the occurrence of dry eye between operated and non-operated eyes. The surgery resulted in increased upper lid margin-reflex distance and consequent decreased eyelid asymmetry, achieving good aesthetic result. However, both amplitude and speed of eyelid movements in operated eyes were lower than those for the control eyes and the surgery was associated with increased risk of dry eye. For this reason, the authors advocate that supramaximal levator resection of the levator palpebrae superioris remains an effective option for the treatment of congenital blepharoptosis, but contraindicate its use in patients with absence of Bell\'s reflex or with previous ocular surface diseases.

Magister Public Health - MPH

Syftet med studien var att genom en litteraturstudie undersöka cigarettröknings påverkan på torra ögon och ögats främre delar. Har cigarettrökning en negativ inverkan på parametrarna för torra ögon? Litteraturstudien genomfördes utifrån sökningar via Web of Science och Pubmed på tidigare kliniska studier och vetenskapliga publikationer. Sökningarna utfördes mellan 2021-03-18 och 2021-03-26. För att specificera sökresultaten skulle artiklarna finnas i fulltext och vara publicerade från år 2016-2021. Sökorden som tillämpades var ”dry eye and smoking” och ”dry eye + smoking”. Studier med färre än 50 deltagare och litteraturstudier/reviews exkluderades. De fem mest relevanta artiklarna utifrån sökresultaten valdes ut för att ingå i studien. Totalt deltog 2692 personer i studierna. Mängden cigarettrökning varierade mellan studierna. Frågeformulären som utfördes var Ocular Surface Disease Index (OSDI) och Mcmonnies Dry Eye Questionnaire (MDEQ), dessa visade en statistisk signifikant skillnad på symptompoäng mellan rökare och icke-rökare i två av fem studier. Det sågs en statistisk signifikant skillnad i Tear Break Up Time (TBUT) mellan testgrupperna i tre av fem studier. Studien visar att cigarettrökning påverkar torra ögon, torra ögonsymptom, ögats främre delar och meibomska körtlarna negativt. Dock ses stora variationer i vad som påverkas inom olika grupper, vilket gör det svårt att fastställa exakt vilken påverkan cigarettrökning har på torra ögon. Fler studier med fler deltagare, ett bestämt antal cigaretter per dag under en bestämd period samt tydliga riktlinjer för utvärdering av DED behövs för att fastställa cigarettröknings påverkan på torra ögon.

No description available.

Purpose The aim of this study was to audit the knowledge and practices regarding eye care and eye complications of diabetes mellitus (DM) among diabetic patients 18 years and above in Kampala, Uganda. Methods. A cross-sectional study was done to collect data on the demographics, level of awareness and practices of the 409 diabetic patients regarding eye care and eye complications of DM. Data collected was captured in EPIDATA version 3.1, exported to STATA version 15.0 for further management and analysis. Participants characteristics were summarized using summary statistics and graphs. Using a standard questionnaire, scores for knowledge and practice for diabetes; knowledge and practice on diabetic retinopathy were generated and in all the four scores aforesaid, participants were classified as having good or poor knowledge and practice1. Proportions of participants demonstrating good awareness and good practice were reported. Fishers and Pearson chi- square tests were used to test for associations between patient’s characteristics and knowledge and practice on DM. Bivariable and logistic regression analysis was performed and variables with a p-value of < 0.2 of the unadjusted odds ratio were further analyzed at multivariate logistic regression analysis to find out factors that significantly predict patient’s knowledge and practice on diabetes mellitus. Results. A total of 409 participants were interviewed in the study, majority were females 293 (71.6%) and mean age (SD) was 50 (12) years. A high proportion of participants 314 (76.9%) was aware that DM could affect the eyes but only 24 (5.9%) stated diabetic retinopathy as an eye complication in diabetic patients. Good knowledge about diabetes mellitus was demonstrated by 178 (43.5%) of the study participants. However, only 33.3% had good knowledge on eye care and diabetic retinopathy. It was determined that female diabetic patients and those who stayed with DM for 10 years and beyond were less likely to have good practice on DM compared to male patients and those who had been with DM for less than five years (OR, 95% CI: 0.58, 0.36-0.95, P=0.029: OR, 95% CI: 0.53, 0.32-0.87, P=0.011). It was also found that diabetic patients with good knowledge of DM were at least three times more likely to have good practice compared to those with the poor knowledge (OR, 95% CI: 3.2, 2.1 -4.8, P <0.001). Conclusion Lack of knowledge regarding the importance and need for periodic eye check-up for diabetic retinopathy was a significant finding in his study. Good knowledge on diabetes, gender and duration of DM had significant association with the patients practice patterns.