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1.  The use of a pre-operative scoring system for the prediction of phacoemulsification case difficulty and the selection of appropriate cases to be performed by trainees 
BMC Ophthalmology  2006;6:38.
Background
To establish whether a previously validated scoring system (Habib) for the prediction of risk or likelihood of posterior capsule rupture during phacoemulsification surgery could be used to: 1. Predict the difficulty of a phacoemulsification case, and 2. Select appropriate phacoemulsification cases for trainees.
Methods
The study sample was consecutive phacoemulsification cases undertaken by senior surgeons at a single ophthalmic unit over a three-week period (170 cases). Each case was scored using a potential difficulty scoring system. Immediately post-operatively, each case was given two scores by the operating surgeon (who was masked with regard to the potential complication score). The first score indicated the perceived difficulty of the case, and the second score, the degree of experience that they thought a trainee would require in order to have performed the same case without complication.
Results
Using Cuzick's non-parametric test for trend, there was evidence for a trend of increasing perceived difficulty with increasing potential difficulty score (p = 0.05), and of increasing experience required with increasing potential difficulty score (p < 0.001)
Conclusion
The authors advocate that Habib's potential difficulty scoring system can be used to inform the surgeon of the likely difficulty of a phacoemulsification case and to aid selection of appropriate cases for trainees prior to surgery.
doi:10.1186/1471-2415-6-38
PMCID: PMC1764898  PMID: 17192173
2.  Hospital Episode Statistics and trends in ophthalmic surgery 1998 – 2004 
BMC Ophthalmology  2006;6:37.
Background
Hospital episode statistics (HES) is a UK national database for the National Health Service (NHS), now available online. The purpose of this study was to observe trends in ophthalmic operations performed during the period from 1998 to 2004, using this data.
Methods
From the 'Main Operation' codes within the 'Free data' section of the HES website we analysed data in regard to 28 specific ophthalmic operations. These represented each sub speciality within ophthalmology.
Results
The figures show a change in the total number and proportions of operations performed for many of the procedures. For example, there was an increase in numbers of orbital decompressions, but a decrease in numbers of glaucoma filtering operations. Changing trends could be seen in different surgical areas such as the change in operations used for corneal grafting and in retinal surgery.
Conclusion
The HES database represents an important, potentially useful source of information. There are imitations in interpretation of and validity of such data related to coding inconsistencies. We suggest the benefit of the data comes from observing trends rather than exact numbers. As other studies using this data have suggested, it is important that clinicians are involved in improving the quality of this data.
doi:10.1186/1471-2415-6-37
PMCID: PMC1698491  PMID: 17144923
3.  Randomised controlled single-blind study of conventional versus depot mydriatic drug delivery prior to cataract surgery 
BMC Ophthalmology  2006;6:36.
Background
A prerequisite for safe cataract surgery is an adequately dilated pupil. The authors conducted a trial to assess the efficacy (in terms of pupil diameter) of a depot method of pre-operative pupil dilatation, as compared with repeated instillations of drops (which is time-consuming for the nursing staff and uncomfortable for the patient).
Methods
A prospective randomised masked trial was conducted comprising 130 patients with no significant ocular history undergoing elective clear corneal phacoemulsification. 65 patients had mydriatic drops (Tropicamide 1%, Phenylephrine 2.5%, Diclofenac sodium 0.1%) instilled prior to surgery, 65 had a wick soaked in the same drop mixture placed in the inferior fornix. Horizontal pupil diameters were recorded on a millimetre scale immediately prior to surgery.
Results
There was no significant difference in pupil size between the two groups (p = 0.255, Student's t-test).
Conclusion
There was no significant difference between the mydriasis obtained with the depot system compared with conventional drop application. Use of a depot mydriatic delivery system appears to be a safe and efficient method of drug delivery.
Trial Registration
International Standard Randomised Controlled Trial Number Register ISRCTN78047760
doi:10.1186/1471-2415-6-36
PMCID: PMC1702365  PMID: 17129389
4.  A technique to train new oculomotor behavior in patients with central macular scotomas during reading related tasks using scanning laser ophthalmoscopy: immediate functional benefits and gains retention 
BMC Ophthalmology  2006;6:35.
Background
Reading with a central scotoma involves the use of preferred retinal loci (PRLs) that enable both letter resolution and global viewing of word. Spontaneously developed PRLs however often privilege spatial resolution and, as a result, visual span is commonly limited by the position of the scotoma. In this study we designed and performed the pilot trial of a training procedure aimed at modifying oculomotor behavior in subjects with central field loss. We use an additional fixation point which, when combined with the initial PRL, allows the fulfillment of both letter resolution and global viewing of words.
Methods
The training procedure comprises ten training sessions conducted with the scanning laser ophthalmoscope (SLO). Subjects have to read single letters and isolated words varying in length, by combining the use of their initial PRL with the one of an examiner's selected trained retinal locus (TRL). We enrolled five subjects to test for the feasibility of the training technique. They showed stable maculopathy and persisting major reading difficulties despite previous orthoptic rehabilitation. We evaluated ETDRS visual acuity, threshold character size for single letters and isolated words, accuracy for paragraphed text reading and reading strategies before, immediately after SLO training, and three months later.
Results
Training the use of multiple PRLs in patients with central field loss is feasible and contributes to adapt oculomotor strategies during reading related tasks. Immediately after SLO training subjects used in combination with their initial PRL the examiner's selected TRL and other newly self-selected PRLs. Training gains were also reflected in ETDRS acuity, threshold character size for words of different lengths and in paragraphed text reading. Interestingly, subjects benefited variously from the training procedure and gains were retained differently as a function of word length.
Conclusion
We designed a new procedure for training patients with central field loss using scanning laser ophthalmoscopy. Our initial results on the acquisition of newly self-selected PRLs and the development of new oculomotor behaviors suggest that the procedure aiming primarily at developing an examiner's selected TRL might have initiated a more global functional adaptation process.
doi:10.1186/1471-2415-6-35
PMCID: PMC1693567  PMID: 17123448
5.  Development and validation of a computerized expert system for evaluation of automated visual fields from the Ischemic Optic Neuropathy Decompression Trial 
BMC Ophthalmology  2006;6:34.
Background
The objective of this report is to describe the methods used to develop and validate a computerized system to analyze Humphrey visual fields obtained from patients with non-arteritic anterior ischemic optic neuropathy (NAION) and enrolled in the Ischemic Optic Neuropathy Decompression Trial (IONDT). The IONDT was a multicenter study that included randomized and non-randomized patients with newly diagnosed NAION in the study eye. At baseline, randomized eyes had visual acuity of 20/64 or worse and non-randomized eyes had visual acuity of better than 20/64 or were associated with patients refusing randomization. Visual fields were measured before treatment using the Humphrey Field Analyzer with the 24-2 program, foveal threshold, and size III stimulus.
Methods
We used visual fields from 189 non-IONDT eyes with NAION to develop the computerized classification system. Six neuro-ophthalmologists ("expert panel") described definitions for visual field patterns defects using 19 visual fields representing a range of pattern defect types. The expert panel then used 120 visual fields, classified using these definitions, to refine the rules, generating revised definitions for 13 visual field pattern defects and 3 levels of severity. These definitions were incorporated into a rule-based computerized classification system run on Excel® software. The computerized classification system was used to categorize visual field defects for an additional 95 NAION visual fields, and the expert panel was asked to independently classify the new fields and subsequently whether they agreed with the computer classification. To account for test variability over time, we derived an adjustment factor from the pooled short term fluctuation. We examined change in defects with and without adjustment in visual fields of study participants who demonstrated a visual acuity decrease within 30 days of NAION onset (progressive NAION).
Results
Despite an agreed upon set of rules, there was not good agreement among the expert panel when their independent visual classifications were compared. A majority did concur with the computer classification for 91 of 95 visual fields. Remaining classification discrepancies could not be resolved without modifying existing definitions.
Without using the adjustment factor, visual fields of 63.6% (14/22) patients with progressive NAION and no central defect, and all (7/7) patients with a paracentral defect, worsened within 30 days of NAION onset. After applying the adjustment factor, the visual fields of the same patients with no initial central defect and 5/7 of the patients with a paracentral defect were seen to worsen.
Conclusion
The IONDT developed a rule-based computerized system that consistently defines pattern and severity of visual fields of NAION patients for use in a research setting.
doi:10.1186/1471-2415-6-34
PMCID: PMC1685661  PMID: 17116264
6.  Optical coherence tomography: an assessment of current training across all levels of seniority in 8 ophthalmic units in the united kingdom 
BMC Ophthalmology  2006;6:33.
Background
Optical Coherence Tomography (OCT) is becoming an increasingly integral part of ophthalmological clinical practice. The accurate interpretation of OCT images is important both in terms of diagnosis and in directing subsequent management. The aim of this study was to determine the clinical competence in OCT image interpretation of ophthalmologists in different subspecialties and grades.
Methods
Eight OCT images demonstrating a single macular pathology and two normal scans were selected by case notes review. These ten images were shown to thirty doctors and 10 non-medical staff from eight units. They were asked to identify each lesion, the average thickness of the lesion, and the axis at which the OCT was taken. One point was awarded for each correct answer.
Results
The mean scores for the correct qualitative identification of the OCT lesion (with a maximum score of 10) for different grades of doctors and non-medical staff were as follows: medical retinal consultants (MRC), 9 (range, 8–10); vitreoretinal consultants (VRC), 7 (range, 6–9); non-retinal consultants (NRC), 4 (range, 2–6); vitreoretinal fellows (VRF), 4 (range, 3–7); specialist registrars (SpR), 3 (range, 2–5); senior house officers (SHO), 4 (range, 3–6); orthoptists, 1 (range, 0–1); ancillary staff, 2 (range, 0–3).
Conclusion
A wide range in the ability to accurately interpret OCT images has been demonstrated. All doctors would thereby benefit from further training in the interpretation of OCT scans.
doi:10.1186/1471-2415-6-33
PMCID: PMC1630698  PMID: 17062159
7.  Bilateral ischemic optic neuropathy after transurethral prostatic resection: a case report 
BMC Ophthalmology  2006;6:32.
Background
Nonarteritic ischemic optic neuropathy affects the anterior portion of the optic nerve and is characterized by sudden, painless visual loss. The affected eye has a relative afferent pupillary defect. The typical funduscopic appearance includes optic disc edema, with associated nerve fiber layer hemorrhage. Risk factors include advanced age, systemic hypertension, nocturnal hypotension, diabetes mellitus, and a small cup-to-disc ratio. Bilateral presentation is rare. Postoperative optic neuropathy has been associated with nonocular surgery; risk factors include a combination of prolonged surgical times, acute systemic hypotension, anemia due to blood loss, or prone positioning. We report for the first time a patient with bilateral, simultaneous anterior ischemic optic neuropathy after elective transurethral prostatic resection.
Case presentation
A 66-year old man underwent surgery for benign prostatic hyperplasia. The preoperative blood pressure was 140/85 mmHg, hemoglobin 15.9 g/dL, and hematocrit 48.6%. Two hours postoperatively, the blood pressure, hemoglobin, and hematocrit dropped dramatically. One day later, transient horizontal diplopia developed. Funduscopy showed a congenitally small cup-to-disc ratio without papillary edema. Other ocular findings were unremarkable. By 4 days postoperatively, sudden and painless amaurosis bilaterally developed when the patient awoke with nausea and vomiting. Visual acuity was no light perception bilaterally. The optic discs were swollen with small hemorrhages. Scans of the head and orbits and electrolyte levels were normal. There were no responses on visual evoked potentials bilaterally. The blood pressure was 90/50 mm Hg, the hemoglobin 7.0 g/dL, and the hematocrit 22.9%, necessitating infusion of three units of packed red blood cells. The blood pressure, hematocrit, and hemoglobin increased to normal levels. Three months later the visual acuity remained no light perception. The pupils were unreactive and there was marked optic disc atrophy bilaterally.
Conclusion
Bilateral and simultaneous acute ischemic optic neuropathy may be a rare but devastating surgical complication. The combination of anemia and hypotension may increase the risk of anterior ischemic optic neuropathy postoperatively after transurethral prostatic resection.
doi:10.1186/1471-2415-6-32
PMCID: PMC1624848  PMID: 17034630
8.  Acute red eye and back pain as a presentation for systemic illness: case report 
BMC Ophthalmology  2006;6:31.
Background
Acute red eye is a common presentation in both primary and secondary care. Presentation in combination with other systemic symptoms can indicate serious underlying pathology.
Case presentation
73-year-old lady presenting with endogenous endophthalmitis and thoracic discitis secondary to sub-acute bacterial endocarditis.
Conclusion
Acute red eye in combination with systemic symptoms requires immediate investigation. If endogenous endophthalmitis is diagnosed, a source of sepsis should be comprehensively investigated and referral made to individual specialities if necessary.
doi:10.1186/1471-2415-6-31
PMCID: PMC1592121  PMID: 16995931
9.  OSCA: a comprehensive open-access system of analysis of posterior capsular opacification 
BMC Ophthalmology  2006;6:30.
Background
This paper presents and tests a comprehensive computerised system of analysis of digital images of posterior capsule opacification (PCO). It updates and expands significantly on a previous presentation to include facilities for selecting user defined central areas and for registering and subsequent merging of images for artefact removal. Also, the program is compiled and thus eliminates the need for specialised additional software. The system is referred to in this paper as the open-access systematic capsule assessment (OSCA). The system is designed to be evidence based, objective and openly available, improving on current systems of analysis.
Methods
Principal features of the OSCA system of analysis are discussed. Flash artefacts are automatically located in two PCO images and the images merged to produce a composite free from these artefacts. For this to be possible the second image has to be manipulated with a registration technique to bring it into alignment with the first. Further image processing and analysis steps use a location-sensitive entropy based texture analysis of PCO. Validity of measuring PCO progression of the whole new system is assessed along with visual significance of scores. Reliability of the system is assessed.
Results
Analysis of PCO by the system shows ability to detect early progression of PCO, as well as detection of more visually significant PCO. Images with no clinical PCO produce very low scores in the analysis. Reliability of the system of analysis is demonstrated.
Conclusion
This system of PCO analysis is evidence-based, objective and clinically useful. It incorporates flash detection and removal as well as location sensitive texture analysis. It provides features and benefits not previously available to most researchers or clinicians. Substantial evidence is provided for this system's validity and reliability.
doi:10.1186/1471-2415-6-30
PMCID: PMC1592309  PMID: 16875500
10.  Bilateral acute angle closure glaucoma as a presentation of isolated microspherophakia in an adult: case report 
BMC Ophthalmology  2006;6:29.
Background
Bilateral simultaneous angle closure glaucoma is a rare entity. To our knowledge this is the first reported case of bilateral acute angle-closure glaucoma secondary to isolated microspherophakia in an adult.
Case presentation
A 45-year-old woman presented with bilateral acute angle closure glaucoma, with a patent iridotomy in one eye. Prolonged miotic use prior to presentation had worsened the pupillary block. The diagnosis was not initially suspected, and the patient was subjected to pars-plana lensectomy and anterior vitrectomy for a presumed ciliary block glaucoma. The small spherical lens was detected intraoperatively, and spherophakia was diagnosed in retrospect. She had no systemic features of any of the known conditions associated with spherophakia. Pars-plana lensectomy both eyes controlled the intraocular pressure successfully.
Conclusion
This case demonstrates the importance of considering the diagnosis of isolated microspherophakia in any case of bilateral acute angle closure glaucoma. Lensectomy appears to be an effective first-line strategy for managing these patients.
doi:10.1186/1471-2415-6-29
PMCID: PMC1526752  PMID: 16827934
11.  Identification of novel mutant PAX6 alleles in Indian cases of familial aniridia 
BMC Ophthalmology  2006;6:28.
Background
Haploinsufficiency at the PAX6 locus causes aniridia, a panocular eye condition characterized by iris hypoplasia and a variety of other anterior and posterior eye defects leading to poor vision. This study was performed to identify novel PAX6 mutations that lead to familial aniridia in Indian patients.
Methods
Genomic DNA was isolated from affected individuals (clinically diagnosed aniridia) from nine unrelated aniridic pedigrees, unaffected family members, and unrelated normal controls. The coding regions of PAX6 were amplified and subjected to single strand conformation polymorphism (SSCP) gel analysis, and direct cloning and sequencing.
Results
SSCP band shifts, indicative of DNA base pair mutations, were observed in five of these unrelated families. Four mutations were shown to be previously unreported insertion or deletions in PAX6, leading to frameshifts. These new mutations were c.1174delTG (in exon 10), c.710delC (exon 6), c.406delTT (exon 5) and c.393insTCAGC (exon 5). The other nonsense mutation, a transition (c.1080C>T) in exon 9, has been reported previously as a mutation hotspot for PAX6 in other ethnic pedigrees. All mutant alleles transmitted through aniridic individuals in each family.
Conclusion
These new deletions and an insertion create frameshifts, which are predicted to introduce premature termination codons into the PAX6 reading frame. The genetic alterations carried by affected individuals are predicted to lead to loss-of-function mutations that would segregate in an autosomal dominant manner to subsequent generations. This is the first report of the 'hotspot' c.1080C>T transition from Indian families.
doi:10.1186/1471-2415-6-28
PMCID: PMC1544350  PMID: 16803629
12.  The prevalence of pseudoexfoliation syndrome in Pakistan. Hospital based study 
BMC Ophthalmology  2006;6:27.
Background
Pseudoexfoliation syndrome (PXS) is the most common identifiable cause of secondary glaucoma, the prevalence of which varies considerably among different ethnicities. The aim of this study was to assess the prevalence of pseudoexfoliation syndrome in Pakistan.
Methods
A prospective study conducted in the period from January 2003 to June 2004 in a teaching hospital serving a population of about 7.6 million. 1860 patients aged 45 or above attending the general ophthalmic clinics were recruited for this study. A detailed evaluation including ophthalmic and general history, slit lamp biomicroscopy, intraocular pressure measurement, gonioscopy and dilated eye examination was performed on all patients.
Results
120(6.45%) subjects were found to have PXS with a male to female ratio of 1.5:1. All 120 (100%) cases were bilateral and 48(40%) patients had high intraocular pressure.
Conclusion
To the best of our knowledge, this is the first study conducted in a Pakistani population to determine the prevalence of PXS. The prevalence rate of 6.45% is similar to other studies conducted in south Asia, however all cases were bilateral and quite a high percentage of patients had high intra-ocular pressure.
doi:10.1186/1471-2415-6-27
PMCID: PMC1513600  PMID: 16792800
13.  The effect of Gonioscopy on keratometry and corneal surface topography 
BMC Ophthalmology  2006;6:26.
Background
Biometric procedures such as keratometry performed shortly after contact procedures like gonioscopy and applanation tonometry could affect the validity of the measurement. This study was conducted to understand the short-term effect of gonioscopy on corneal curvature measurements and surface topography based Simulated Keratometry and whether this would alter the power of an intraocular lens implant calculated using post-gonioscopy measurements. We further compared the effect of the 2-mirror (Goldmann) and the 4-mirror (Sussman) Gonioscopes.
Methods
A prospective clinic-based self-controlled comparative study. 198 eyes of 99 patients, above 50 years of age, were studied. Exclusion criteria included documented dry eye, history of ocular surgery or trauma, diabetes mellitus and connective tissue disorders. Auto-Keratometry and corneal topography measurements were obtained at baseline and at three follow-up times – within the first 5 minutes, between the 10th-15th minute and between the 20th-25th minute after intervention. One eye was randomized for intervention with the 2-mirror gonioscope and the other underwent the 4-mirror after baseline measurements. t-tests were used to examine differences between interventions and between the measurement methods. The sample size was calculated using an estimate of clinically significant lens implant power changes based on the SRK-II formula.
Results
Clinically and statistically significant steepening was observed in the first 5 minutes and in the 10–15 minute interval using topography-based Sim K. These changes were not present with the Auto-Keratometer measurements. Although changes from baseline were noted between 20 and 25 minutes topographically, these were not clinically or statistically significant. There was no significant difference between the two types of gonioscopes. There was greater variability in the changes from baseline using the topography-based Sim K readings.
Conclusion
Reversible steepening of the central corneal surface is produced by the act of gonioscopy as measured by Sim K, whereas no significant differences were present with Auto-K measurements. The type of Gonioscope used does not appear to influence these results. If topographically derived Sim K is used to calculate the power of the intraocular lens implant, we recommend waiting a minimum of 20 minutes before measuring the corneal curvature after gonioscopy with either Goldmann or Sussman contact lenses.
doi:10.1186/1471-2415-6-26
PMCID: PMC1550259  PMID: 16780595
14.  Patient-centred measurement in ophthalmology – a paradigm shift 
BMC Ophthalmology  2006;6:25.
Ophthalmologists and researchers in ophthalmology understand what a rapidly evolving field ophthalmology is, and that to conduct good research it is essential to use the latest and best methods. In outcomes research, one modern initiative has been to conduct holistic measurement of outcomes inclusive of the patient's point of view; patient-centred outcome. This, of course, means including a questionnaire. However, the irony of trying to improve outcomes research by being inclusive of many measures is that the researcher may not be expert in all measures used. Certainly, few people conducting outcomes research in ophthalmology would claim to be questionnaire experts. Most tend to be experts in their ophthalmic subspecialty and probably simply choose a popular questionnaire that appears to fit their needs and think little more about it. Perhaps, unlike our own field, we assume that the field of questionnaire research is relatively stable. This is far from the case. The measurement of patient-centred outcomes with questionnaires is a rapidly evolving field. Indeed, over the last few years a paradigm shift has occurred in patient-centred measurement.
doi:10.1186/1471-2415-6-25
PMCID: PMC1538625  PMID: 16774690
15.  Is the NEI-VFQ-25 a useful tool in identifying visual impairment in an elderly population? 
BMC Ophthalmology  2006;6:24.
Background
The use of self-report questionnaires to substitute for visual acuity measurement has been limited. We examined the association between visual impairment and self reported visual function in a population sample of older people in the UK.
Methods
Cross sectional study of people aged more than 75 years who initially participated in a trial of health screening. The association between 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ) scores and visual impairment (defined as an acuity of less than 6/18 in the better eye) was examined using logistic regression.
Results
Visual acuity and NEI-VFQ scores were obtained from 1807 participants (aged 77 to 101 years, 36% male), from 20 general practices throughout the UK. After adjustment for age, gender, practice and NEI-VFQ sub-scale scores, those complaining of poor vision in general were 4.77 times (95% CI 3.03 to 7.53) more likely to be visually impaired compared to those who did not report difficulty. Self-reported limitations with social functioning and dependency on others due to poor vision were also associated with visual impairment (odds ratios, 2.52, 95% CI 1.55 to 4.11; 1.73, 95% CI 1.05 to 2.86 respectively). Those reporting difficulties with near vision and colour vision were more likely to be visually impaired (odds ratios, 2.32, 95% CI 1.30 to 4.15; 2.25, 95% CI 1.35 to 3.73 respectively). Other NEI-VFQ sub-scale scores were unrelated to measures of acuity. Similar but weaker odds ratios were found with reduced visual acuity (defined as less than 6/12 in the better eye). Although differences in NEI-VFQ scores were small, scores were strongly associated with visual acuity, binocular status, and difference in acuity between eyes.
Conclusion
NEI-VFQ questions regarding the quality of general vision, social functioning, visual dependency, near vision and colour vision are strongly and independently associated with an objective measure of visual impairment in an elderly population.
doi:10.1186/1471-2415-6-24
PMCID: PMC1523367  PMID: 16764714
16.  Lutein supplementation in retinitis pigmentosa: PC-based vision assessment in a randomized double-masked placebo-controlled clinical trial [NCT00029289] 
BMC Ophthalmology  2006;6:23.
Background
There is no generally accepted medical or surgical treatment to stop the progressive course of retinitis pigmentosa. Previous studies have suggested lutein as a potential treatment with positive effects on macular pigment density. The objective of this study was to examine the effect of lutein supplementation on preservation of visual function in patients with retinitis pigmentosa (RP)
Methods
In a double-masked randomized placebo-controlled phase I/II clinical trial with a cross-over design, 34 adult patients with RP were randomized to two groups. One group, consisted of 16 participants, received lutein supplementation (10 mg/d for 12 wks followed by 30 mg/d) for the first 24 weeks and then placebo for the following 24 weeks, while the other group included 18 participants for whom placebo (24 weeks) was administered prior to lutein. Visual acuity, contrast sensitivity, and central visual field were measured at different illumination levels at baseline and every week using a PC-based test at home.
Results
For visual acuity (VA) at normal illumination level, treatment with lutein reduced logMAR, i.e. improved VA, but this effect was not statistically significant. The changes in normal (100%), low (4%), and very low (0.1%) illumination log CS were not statistically significant (p-values: 0.34, 0.23, and 0.32, respectively). Lutein had a statistically significant effect on visual field (p-value: 0.038) and this effect increased in the model assuming a 6-week delay in effect of lutein. Comparing the development of vision measures against the natural loss expected to occur over the course of 48 weeks, most measures showed reduced decline, and these reductions were significant for normal illumination VA and CS.
Conclusion
These results suggest that lutein supplementation improves visual field and also might improve visual acuity slightly, although these results should be interpreted cautiously. As a combined phase I and II clinical trial, this study demonstrated the efficacy and safety of lutein supplementation.
doi:10.1186/1471-2415-6-23
PMCID: PMC1522015  PMID: 16759390
17.  Efficacy of topical cobalt chelate CTC-96 against adenovirus in a cell culture model and against adenovirus keratoconjunctivitis in a rabbit model 
BMC Ophthalmology  2006;6:22.
Background
Adenovirus (Ad), associated with significant morbidity, has no topical treatment. A leading CTC compound (CTC-96), a CoIII chelate, was found to have potent in vitro and in vivo antiviral efficacy against herpes viruses. In this study CTC-96 is being tested for possible anti-Adenovirus activity.
Methods
The biological anti-adenovirus activity of CTC-96 in concentrations from 5 to 250 ug/ml, was evaluated initially by viral inactivation (viral exposure to CTC-96 followed by dilution and inoculation of cells), virucidal (viral exposure to CTC-96 and inoculation of cells without dilution) and antiviral (effect of CTC-96 on previously adsorbed virus) plaque assays on HeLa (human cervical carcinoma), A549 (human lung carcinoma) and SIRC (rabbit corneal) cells. After verifying the antiviral activity, New Zealand White rabbits were infected with Ad-5 into: 1) the anterior cul-de-sac scarifying the conjunctiva (Group "C+"); 2) the anterior cul-de-sac scarifying the conjunctiva and cornea (Group "CC+"); 3) the stroma (Group "CI+"). Controls were sham-infected ("C-", "CC-", "CI-"). Other rabbits, after "CC", were treated for 21 days with: 1) placebo, 9x/day ("-"); 2) CTC-96, 50 ug/ml, 9x/day ("50/9"); CTC-96, 50 ug/ml, 6x/day ("50/6"); CTC-96, 25 ug/ml, 6x/day ("25/6"). All animals were monitored via examination and plaque assays.
Results
In vitro viral inactivation, virucidal and antiviral assays all demonstrated CTC-96 to be effective against Adenvirus type 5 (ad-5). The in vivo model of Ad keratoconjunctivitis most similar to human disease and producing highest viral yield was "CC". All eyes (6/6) developed acute conjunctivitis. "CI" yielded more stromal involvement (1/6) and iritis (5/6), but lower clinical scores (area × severity). Infection via "C" was inconsistent (4/6). Fifty (50) ug/ml was effective against Ad-5 at 6x, 9x dosings while 25 ug/ml (6x) was only marginally effective.
Conclusion
CTC-96 demonstrated virucidal activity against Ad5 in tissue culture with HeLa, A549 and SIRC cell lines.
Animal Model Development: 1) "CC" produced conjunctival infection with occasional keratitis similar to human disease; "CI" yielded primarily stromal involvement; 2) "C" consistently produced neither conjunctivitis nor keratitis.
CTC Testing: 1) Conjunctivitis in all eyes; 2) Resolution fastest in "50/9" ("50/9". "50/6" > "25/6" > "-"); 3) Efficacy in "50/6" was not statistically different than "50/9"; 4) Conjunctival severity was lower in treatment groups then controls; 5) Little corneal or intra-ocular changes were noted.
doi:10.1186/1471-2415-6-22
PMCID: PMC1502138  PMID: 16753060
18.  Comparison of silicon oil removal with various viscosities after complex retinal detachment surgery 
BMC Ophthalmology  2006;6:21.
Background
Despite the progress in vitreoretinal surgery and the importance of silicone oil as an adjunct for the treatment of complex forms of retinal detachment, controversy still surrounds the issue of selecting the proper oil viscosity for clinical use. Herein, we evaluate the outcomes of retinal detachment (RD) surgery after removing silicone oils of different viscosities.
Methods
In this retropsective cohort study, eighty-two eyes with surgically re-attached retinas, of which 53 were filled with 5000cs silicone oil and 29 with 1000cs silicone oil were enrolled. We evaluated the outcomes and complications following silicone oil removal. Final anatomic success (stable re-attachment), final visual acuity (VA) and intraocular pressure (IOP)were recorded and analysed.
Results
Of 82 eyes, 41 had proliferative vitreoretinopathy (PVR), 24 were associated with intraocular foreign bodies, 10 had endophthalmitis and 7 had proliferative diabetic retinopathy with tractional retinal detachment. Prior to silicone oil removal, the retina was attached in all eyes, 29% had VA ≥ 6/120 and 52% had IOP ≥ 21 mmHg. After silicone oil removal, the retina remained attached in 59(72%) of the eyes, 34% had VA ≥ 6/120 and 9% had IOP ≥ 21 mmHg. Comparing 1000cs and 5000cs silicone oil filled eyes, redetachment occurred more frequently in the latter group especially in cases with associated PVR. Final VA worse than 6/120 was associated with initial VA < 6/120 (OR = 32.2 95%CI 7.4–140.2) and use of 5000cs silicone oil (OR = 7.9 95%CI 1.9–32.2). No factor was significantly associated with final IOP ≥ 21 mmHg.
Conclusion
In complicated retinal detachment surgery, use of 5000cs silicone oil may be associated with a poorer anatomic and visual outcome compared with 1000cs silicone oil. However there was no difference between the two viscosities in IOP elevation. A randomized controlled study is necessary to further evaluate such a possibility.
doi:10.1186/1471-2415-6-21
PMCID: PMC1501055  PMID: 16737520
19.  Fluorophotometry as a diagnostic tool for the evaluation of dry eye disease 
BMC Ophthalmology  2006;6:20.
Background
Dry eye disease is a common debilitating ocular disease. Current diagnostic tests used in dry eye disease are often neither sensitive nor reproducible, making it difficult to accurately diagnose and determine end points for clinical trials, or evaluate the usefulness of different medications in the treatment of dry eye disease. The recently developed fluorophotometer can objectively detect changes in the corneal epithelium by quantitatively measuring its barrier function or permeability. The purpose of the study is to investigate the use of corneal fluorescein penetration measured by the fluorophotometer as a diagnostic tool in the evaluation of dry eye patients.
Methods
Dry eye patients (16 eyes), who presented with a chief complaint of ocular irritation corresponding with dry eye, low Schirmer's one test (<10 mm after 5 minutes) and corneal fluorescein staining score of more than two, were included in the study. Normal subjects (16 eyes), who came for refraction error evaluation, served as controls. Institutional Review Board (IRB) approved consent was obtained before enrolling the subjects in the study and all questions were answered while explaining the risks, benefits and alternatives. All Fluorophotometry of the central corneal epithelium was done utilizing the Fluorotron Master (TradeMark). Each eye had a baseline fluorescein scan performed, after which 50 l of 1% sodium fluorescein dye was instilled. Three minutes later, the fluorescein was washed with 50 ml of normal saline. Fluorescein scans were then started immediately after washing and were recorded at 10, 20, 40, and 60 minutes thereafter. The corneal peak values of fluorescein concentration were recorded within the central cornea in both dry eyes and in controls.
Results
Ten minutes after fluorescein installition, patients with dry eye disease averaged a five-fold increase in corneal tissue fluorescein concentration (mean = 375.26 ± 202.67 ng/ml) compared with that of normal subjects (mean = 128.19 ± 85.84 ng/ml). Sixty minutes after dye installation, patients with dry eye disease still revealed higher corneal tissue fluorescein concentration (mean = 112.87 ± 52.83 ng/ml) compared with that of controls (mean = 40.64 ± 7.96 ng/ml), averaging a three-fold increase.
Conclusion
Patients with dry eye disease demonstrated an increased corneal permeability and a slower rate of elimination to topically administered fluorescein when measured by the fluorophotometer. This suggests that fluorophotometry may serve as a valuable quantitative and objective tool for the diagnosis of dry eye disease, and in following patients' response to new treatment modalities. Fluorophotometry may serve as an objective non-invasive tool for end-point analysis in clinical trials of new treatments for dry eye disease.
doi:10.1186/1471-2415-6-20
PMCID: PMC1523366  PMID: 16729882
20.  Hyeropic shift after LASIK induced Diffuse lamellar keratitis 
BMC Ophthalmology  2006;6:19.
Background
Diffuse lamellar keratitis (DLK) is a relatively new syndrome that is increasingly being reported after LASIK. We have observed that a hyperopic shift may be associated with the occurrence of this diffuse lamellar keratitis.
Case presentation
A 26 year old man developed bilateral diffuse lamellar keratitis (DLK) following myopic LASIK. The residual refractive error was +0.5D OD and +0.25D OS at the end of the first week. The sterile infiltrates resolved over a period of 4–6 weeks on topical steroid therapy. A progressive hyperopic shift was noted in the right eye with an error +4.25Dsph/+0.25Dcyl 20 at the final follow up 6 months post surgery.
Conclusion
Diffuse lamellar keratitis after LASIK may be associated with a significant hyperopic shift.
doi:10.1186/1471-2415-6-19
PMCID: PMC1501054  PMID: 16646976
21.  Comparison of age-specific cataract prevalence in two population-based surveys 6 years apart 
BMC Ophthalmology  2006;6:17.
Background
In this study, we aimed to compare age-specific cortical, nuclear and posterior subcapsular (PSC) cataract prevalence in two surveys 6 years apart.
Methods
The Blue Mountains Eye Study examined 3654 participants (82.4% of those eligible) in cross-section I (1992–4) and 3509 participants (75.1% of survivors and 85.2% of newly eligible) in cross-section II (1997–2000, 66.5% overlap with cross-section I). Cataract was assessed from lens photographs following the Wisconsin Cataract Grading System. Cortical cataract was defined if cortical opacity comprised ≥ 5% of lens area. Nuclear cataract was defined if nuclear opacity ≥ Wisconsin standard 4. PSC was defined if any present. Any cataract was defined to include persons who had previous cataract surgery. Weighted kappa for inter-grader reliability was 0.82, 0.55 and 0.82 for cortical, nuclear and PSC cataract, respectively. We assessed age-specific prevalence using an interval of 5 years, so that participants within each age group were independent between the two surveys.
Results
Age and gender distributions were similar between the two populations. The age-specific prevalence of cortical (23.8% in 1st, 23.7% in 2nd) and PSC cataract (6.3%, 6.0%) was similar. The prevalence of nuclear cataract increased slightly from 18.7% to 23.9%. After age standardization, the similar prevalence of cortical (23.8%, 23.5%) and PSC cataract (6.3%, 5.9%), and the increased prevalence of nuclear cataract (18.7%, 24.2%) remained.
Conclusion
In two surveys of two population-based samples with similar age and gender distributions, we found a relatively stable cortical and PSC cataract prevalence over a 6-year period. The increased prevalence of nuclear cataract deserves further study.
doi:10.1186/1471-2415-6-17
PMCID: PMC1524813  PMID: 16623958
22.  Cataract surgery by appointment – a pilot study 
BMC Ophthalmology  2006;6:18.
Background
"Cataract Surgery by Appointment" is a new method of delivery of cataract surgery that reduces the time a patient spends in hospital by their direct arrival at the operating theatre, having self-prepared for surgery, thus avoiding admission to the ward or time spent in the Day Case Unit. The patient can stay as little as 20 minutes from their arrival to going home. We describe the process in detail, and seek to evaluate the visual outcome, safety and patient satisfaction of same.
Methods
Visual outcome and safety data were obtained from patients' medical records, prospectively. Patients were also surveyed by a questionnaire to determine their satisfaction with the service and viability as a prospect for providing a more efficient cataract surgery service.
Results
In 2002, fifty-one eyes of 39 consecutive patients underwent "Cataract Surgery by Appointment". There were 16 male and 23 female. The pre-operative best-corrected visual acuity was 6/9 or better in 17 (33%) eyes. The post-operative best-corrected visual acuity was 6/9 or better in 44 (86%) eyes. There were no per-operative complications. Post-operative complications occurred in 3 (6%) eyes. The average number of days from surgery to final discharge was 14.5 days.
Twenty-eight (72%) completed questionnaires were returned. The results show that the majority of patients were satisfied with their overall experience of this mode of delivery for cataract surgery.
Conclusion
"Cataract Surgery by Appointment" performed under local anaesthesia by a skilled ophthalmic surgeon appears to be safe and effective for highly selected cases. This method of delivery gave a high level of patient satisfaction, and is the ultimate form of day case cataract surgery. The method may gain widespread use should per-operative intracameral pupil dilatation prove to be effective and acceptable. Attention should be paid to risk-stratification, so complex cases are allocated more time on the operating list.
doi:10.1186/1471-2415-6-18
PMCID: PMC1459203  PMID: 16626495
23.  Early lens aging is accelerated in subjects with a high risk of ischemic heart disease: an epidemiologic study 
BMC Ophthalmology  2006;6:16.
Background
Ischemic heart disease (IHD) is one of the most important causes of mortality and morbidity in the Western world. There is a relationship between aging of the lens of the human eye and cardiovascular disease. The present study was conducted to examine if the risk of ischemic heart disease could be estimated by fluorophotometric assessment of lens aging.
Methods
A total of 421 subjects were included. Risk of IHD was estimated from non-ocular data using the Precard ® software. Lens aging was quantified by lens fluorometry.
Results
The risk of IHD was strongly related to lens fluorophore accumulation (p = 0.001). The relationship between IHD and lens aging was attributable to tobacco smoking and dysglycemia.
Conclusion
The risk of ischemic heart disease related to smoking and diabetes mellitus can be estimated using the aging of the lens of the eye as a biomarker for generalized tissue-damage.
doi:10.1186/1471-2415-6-16
PMCID: PMC1459876  PMID: 16618373
24.  The effect of posterior subtenon methylprednisolone acetate in the refractory diabetic macular edema: a prospective nonrandomized interventional case series 
BMC Ophthalmology  2006;6:15.
Background
To investigate the efficacy of posterior subtenon methylprednisolone acetate injection in treatment of refractory diffuse clinically significant diabetic macular edema (CSME).
Methods
In a prospective, nonrandomized, interventional case series, 52 eyes were diagnosed with CSME and treated with at least two sessions of laser photocoagulation according to Early Treatment Diabetic Retinopathy Study guidelines. At least 3 months after laser therapy, eyes with a residual central macular thickness were offered posterior subtenon injection of 40 mg methylprednisolone acetate. Main outcome measures were visual acuity, macular thickness and intraocular pressure. Potential complications were monitored, including intraocular pressure response, cataract progression and scleral perforation.
Results
Mean baseline visual acuity (in logMAR) improved significantly (p = 0.003) from 0.8 ± 0.36 to 0.6 ± 0.41 at 3 months. Mean foveal thickness decreased from 388 ± 78 μm at baseline to 231 ± 40 μm after 3 months (p < 0.0001). Visual acuity improvement in eyes with CSME with extrafoveal hard exudates was significant (p = 0.0001), but not significant in eyes with CSME with subfoveal hard exudates (p = 0.32). Intraocular pressure increased from 14.7 ± 2.0 mmHg (range, 12–18 mmHg) to a maximum value of 15.9 ± 2.1 mmHg (range, 12–20 mmHg) during the follow-up period. Complications in two eyes developed focal conjunctival necrosis at the site of injection.
Conclusion
Posterior subtenon methylprednisolone acetate may improve early visual outcome in diffuse diabetic macular edema that fails to respond to conventional laser photocoagulation. Visual acuity improvement in eyes with CSME with extrafoveal hard exudates was significant; and this improvement is depends on location of hard exudates. Further study is needed to assess the long-term efficacy, safety, and retreatment.
doi:10.1186/1471-2415-6-15
PMCID: PMC1524812  PMID: 16595011
25.  Insertion of a foldable hydrophobic IOL through the trabeculectomy fistula in cases with Microincision cataract surgery combined with trabeculectomy 
BMC Ophthalmology  2006;6:14.
Background
The use of conventional foldable hydrophobic intraocular lenses (IOLs) in microincision cataract surgery (MICS) currently requires wound enlargement. We describe a combined surgical technique of MICS and trabeculectomy with insertion of a foldable IOL through the trabeculectomy fistula.
Methods
After completion of MICS through two side port incisions, a 3.2 mm keratome is used to enter the anterior chamber under the previously outlined scleral flap. An Acrysof multi piece IOL (Alcon labs, Fort Worth, Tx) is inserted into the capsular bag through this incision. The scleral flap is then elevated and a 2 × 2 mm fistula made with a Kelly's punch. The scleral flap and conjunctival closure is performed as usual.
Results
Five patients with primary open angle glaucoma with a visually significant cataract underwent the above mentioned procedure. An IOL was implated in the capsular bag in all cases with no intraperative complications. After surgery, all patients obtained a best corrected visual acuity of 20/20, IOL was well centered at 4 weeks follow up. The mean IOP (without any antiglaucoma medication) was 13.2 + 2.4 mm Hg at 12 weeks with a well formed diffuse filtering bleb in all the cases.
Conclusion
The technique of combining MICS with trabeculectomy and insertion of a foldable IOL through the trabeculectomy fistula is a feasible and valuable technique for cases which require combined cataract and glaucoma surgery.
doi:10.1186/1471-2415-6-14
PMCID: PMC1471801  PMID: 16545141

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