Relationship Between Intraocular Pressure and Age: A Population-Based Study in Nepal.

PRCIS: Intraocular pressure (IOP) decreased with age in a population-based study in Nepal, from a mean of 14.1 mm Hg among those 60-64 years old to 13.0 mm Hg among those 80 years old or older. PURPOSE: Few studies have assessed the distribution of IOP from the Indian subcontinent, despite its large population and high burden of glaucoma. The objective of this study was to assess the distribution of IOP measurements from adults living in a lowland region of Nepal. METHODS: In a population-based cross-sectional study, all individuals aged 60 years and older from an area of lowland Nepal were invited for an IOP assessment with a rebound tonometer. RESULTS: Of 160 communities (28,672 people aged ≥60 y) enrolled, 79 (13,808 people aged ≥60 y) were randomly selected for IOP testing. Of those eligible, 10,017 (72.5%) individuals underwent tonometry. Mean IOP decreased monotonically over 5-year age groups, from 14.1 mm Hg (SD: 3.6) among those aged 60-64 years to 13.0 mm Hg (SD: 4.2) among those 80 years or older. The 97.5th percentile IOP measurement was 21.0 mm Hg for all age groups. In adjusted analyses, younger age, self-reported diabetes, and higher population density were each associated with higher IOP, and self-reported cataract surgery was associated with lower IOP. CONCLUSIONS: Mean IOP was lower among older individuals in Nepal, consistent with many studies from East Asia and in contrast to many studies from western populations. These results suggest that ethnic background might be a consideration when diagnosing ocular hypertension.

Prevalence of treatment with glaucoma medication in Scotland, 2010-2017.

AIMS: To report the number and demographic distribution of patients receiving intraocular pressure (IOP)-lowering medications across the whole population of Scotland for the years 2010-2017 and, using national census data, show how the observed changes compare with those predicted by the increasing age of the population structure over this period. METHODS: Data were sourced from the Prescribing Information System of the NHS Information and Statistics Division for Scotland. The number of patients dispensed any IOP-lowering medication from a community pharmacy during each calendar year was collected by gender and by 5-year age bands. National census data were used to model the expected annual increase in treatment numbers due to population ageing. RESULTS: The number of treated patients in 2017 was 61 249 which represents 1.13% of the whole population (or 2.16% over 40 years of age). The number increased from 48 178 in 2010-an increase over this period of 27.13% (3.88% per year).Prevalence increased with age, reaching 10.67% in those over 90 years. After age adjustment, more men were treated than women (OR 1.26).The expected number treated in 2017 based on census predictions was 54 075 (an increase of 5897 (12.24%) from 2010). The observed growth of 27.13% was 2.22-fold greater than the rate expected by population changes over the period 2010-2017. CONCLUSION: The number of patients on medication for glaucoma and ocular hypertension in Scotland is increasing. The rate of increase cannot be explained by changes in the size and age structure of the population alone.

Cataract surgery refractive outcomes: representative standards in a National Health Service setting.

BACKGROUND/AIMS: To report refractive outcomes from an National Health Service (NHS) cataract surgery service and assess if results meet suggested benchmark standard. METHODS: Details of all patients undergoing cataract surgery in the Southern General and New Victoria hospitals in Glasgow, UK, between November 2006 and December 2016 were prospectively entered into an electronic database. Patients were reviewed 4 weeks postoperatively in the eye clinic and underwent refraction at their local optometrist prior to this appointment. Surgically uncomplicated cases with in the bag' non-toric intraocular lens implantation were included. Patients with previous laser refractive procedures or failing to achieve 6/12 acuity or better postoperatively were excluded. Proximity to targeted postoperative refraction was documented. RESULTS: Over this 10-year period, 11 083 eyes underwent cataract surgery. Of these, 8943 eyes of 6936 patients (80.69%) met the inclusion criteria and had both target and postoperative outcome refraction recorded. The mean difference between the targeted and outcome refraction was -0.07 D (SD 0.67). The mean absolute error was 0.50 D. Postoperative refraction was within 1 D of target refraction for 7938 eyes (88.76%) and within 0.50 D for 5577 eyes (62.36%). CONCLUSION: Refractive outcomes following routine cataract surgery reported here are well within the targets recommended by the Royal College of Ophthalmologists and European guidelines, but suggest that higher cataract refractive outcome benchmark standards may not yet be a realistic expectation for all NHS units with current biometry practice.

Outcome of repeat trabeculectomies: long-term follow-up.

AIM: To assess medium-term to long-term outcomes of a cohort of repeat trabeculectomy augmented with mitomycin C (MMC). METHODS: A prospective evaluation of consecutive separate site repeat MMC-augmented trabeculectomies undertaken at a single institution between October 2000 and December 2012. Information regarding visual acuity (VA), intraocular pressure (IOP), visual field progression, postoperative interventions, surgery complications and success of surgery are presented.Complete and qualified (ie, with or without glaucoma medication) success rates were presented on the basis of three levels of IOP control: ≤21, ≤17 and ≤14 mm Hg without hypotony or reoperation. RESULTS: Fifty-six eyes of 56 patients were evaluated. Thirty-seven per cent of the cohort had a previously augmented trabeculectomy. Mean follow-up was 6.3±3.4 years. At 60-month follow-up, 56.1% of patients achieved complete success and 75.6% achieved qualified success at the ≤21 mm Hg target. Complete and qualified success rates were 53.7% and 73.2%, respectively at the ≤17 mm Hg target and 51.2% and 61.0%, respectively at the ≤14 mm Hg target. Mean preoperative IOP was 29.1±6.0 mm Hg. At the 60-month follow-up visit the mean IOP was 12.6±4.7 mm Hg. Requirement for topical medications dropped from a mean of 2.9 to 0.5 per patient. No medications were required in 68.3%. CONCLUSIONS: Safe repeat trabeculectomy technique with antimetabolite titrated against the individual patients risk profile can result in improved results in the medium-term to long-term.

Validity of the Monocular Trial of Intraocular Pressure-Lowering at Different Time Points in Patients Starting Topical Glaucoma Medication.

IMPORTANCE: Establishing the true therapeutic effect of eyedrops when initiating glaucoma therapy is important. Accurate prediction of the intraocular pressure (IOP)-lowering response in the fellow eye when using a monocular trial eliminates the need for additional office visits to confirm the therapeutic effect. OBJECTIVE: To investigate the validity of the monocular trial in patients commencing topical glaucoma treatment at different time points. DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study of untreated patients with open-angle glaucoma or ocular hypertension at a hospital-based glaucoma service among treatment-naive individuals. The study dates were October 1, 2008, to November 30, 2009. INTERVENTIONS: Participants had 8 visits. After the recruitment visit, IOP was measured in both eyes by masked applanation tonometry at 8 am, 11 am, and 4 pm for 7 consecutive weeks. Treatment with travoprost, 0.004%, was commenced at week 3 in the trial eye and at week 4 in the fellow eye. MAIN OUTCOMES AND MEASURES: Three IOP outcomes were measured for the trial eye, including unadjusted IOP-lowering effect, adjusted IOP-lowering effect, and true therapeutic effect. RESULTS: Of 30 topical glaucoma treatment-naive individuals (11 male and 19 female), 16 had ocular hypertension and 14 had primary open-angle glaucoma. Their mean (SD) age was 64.4 (12.6) years (age range, 42-88 years). The unadjusted IOP-lowering effect overestimated the true therapeutic effect by mean (SD) 2.5 (4.8), 3.1 (3.8), and 4.9 (4.4) mm Hg at 8 am, 11 am, and 4 pm, respectively, and the mean (SD) adjusted IOP-lowering effect was almost identical to the true therapeutic effect at each of the 3 time points (0.43 [3.87], 0.02 [2.82], and -0.40 [3.90]), respectively. The correlation between the unadjusted effect of treatment and the true therapeutic effect was 0.55 (95% CI, 0.23-0.76), and the effect when adjusted by the monocular trial was 0.72 (95% CI, 0.49-0.86). Fellow eye responses to treatment were correlated at all time points (r range, 0.78-0.86). Treatment did not demonstrate any effect on the diurnal pattern of IOP. CONCLUSIONS AND RELEVANCE: The monocular trial of therapy is effective in accurately predicting the response of an untreated eye to monotherapy with a prostaglandin analogue at all daytime time points measured. There is no requirement for patients to be seen at the same time of day after treatment has commenced. The effect in the first eye predicts both the likelihood and magnitude of an effect in the second eye at all time points during office hours and negates the requirement for an additional visit to check the therapeutic effect when commencing therapy in the second eye.

Glaucoma-service provision in Scotland: introduction and need for Scottish Intercollegiate Guidelines Network guidelines.

PURPOSE: To describe the pattern of glaucoma-service delivery in Scotland and identify areas for improvement, taking into account Scottish General Ophthalmic Services (GOS) arrangements and the Eye Care Integration project, and to design Scottish Intercollegiate Guidelines Network (SIGN) guidelines to refine the primary and secondary interface of glaucoma care. MATERIALS AND METHODS: A glaucoma-survey questionnaire was sent to all consultant glaucomatologists in Scotland. The design of SIGN guidelines was based on the results of the questionnaire using SIGN methodology. RESULTS: Over 90% of Scottish glaucoma care is triaged and delivered within hospital services. Despite GOS referral, information is variable. There are no consistent discharge practices to the community. These results led to defined research questions that were answered, thus formulating the content of the SIGN guidelines. The guideline covers the assessment of patients in primary care, referral criteria to hospital, discharge criteria from hospital to community, and monitoring of patients at risk of glaucoma. CONCLUSION: With increasing age and limitations to hospital resources, refining glaucoma pathways between primary and secondary care has become a necessity. Scotland has unique eye care arrangements with both the GOS and Eye Care Integration project. It is hoped that implementation of SIGN guidelines will identify glaucoma at the earliest opportunity and reduce the rate of false-positive referrals to hospital.

Repeatability of measurements of effectiveness of glaucoma medication.

AIMS: To determine short-term repeatability of the effect of intraocular pressure (IOP) reducing medication and the number of repeated measurements necessary to estimate therapeutic effect with a given degree of precision. METHODS: IOP was measured at 8:00, 11:00 and 16:00 h at each of three weekly visits in untreated patients with primary open-angle glaucoma or ocular hypertension. After starting travaprost (0.004%) to both eyes, the measurements were repeated for a further three weekly visits. Repeatability of the change in IOP 1, 2 and 3 weeks after starting treatment was reported as the coefficient of repeatability (CR) and coefficient of variability (CV). RESULTS: Mean reduction in IOP was 7.5 mm Hg (29.9%). CR and CV between visits were 7.8 mm Hg and 37.2%, respectively. Repeated estimates of the effectiveness of treatment in the same subject at the same time of day would, therefore, be expected to lie within a range of 7.8 mm Hg and within ±73.2% of the mean effect with 95% confidence. A reduction in IOP less than 7.8 mm Hg over a single pair of measurements would be indistinguishable from measurement error. Precision improves from ±73.2% for a single pair of readings to ±25.9% for eight pairs. CONCLUSIONS: Day-to-day repeatability in the estimation of medication effectiveness is poor even for time-of-day standardised measurements and the number of IOP measurements required to achieve precision adequate for use in clinical practice is large.

Day-to-day variability in intraocular pressure in glaucoma and ocular hypertension.

AIMS: To investigate the day-to-day repeatability of intraocular pressure (IOP) measurements. METHODS: A prospective cohort study of untreated patients presenting with primary open-angle glaucoma or ocular hypertension presenting with IOP>21 mm Hg. IOP was measured by masked Goldmann tonometry at 08:00, 11:00 and 16:00 at each of the three weekly visits. After starting travaprost (0.004%) to both eyes, the measurements were repeated for a further three weekly visits. Day-to-day repeatability was estimated before and after commencing medication and reported as the coefficient of repeatability and coefficient of variability. RESULTS: At the 8:00 time point, mean IOPs were 26.1 and 17.9 mm Hg in the eye with higher pressure before and after starting treatment, respectively. Coefficient of repeatability and coefficient of variability were 6.8 mm Hg and 10.0%, respectively, before treatment, and 4.6 mm Hg and 10.5% on treatment. Therefore, before treatment and after starting medication the IOP lay within a range of ±20% of the mean IOP with 95% confidence. CONCLUSIONS: The non-therapeutic variability from day to day significantly undermines the precision of IOP estimation and of the estimation of medication effectiveness even when the time of day is standardised in patients with primary open-angle glaucoma/ocular hypertension.

Monocular trial of intraocular pressure-lowering medication: a prospective study.

OBJECTIVE: To investigate the validity of the monocular therapeutic trial of therapy in patients commencing topical glaucoma treatment. DESIGN: Prospective intention-to-treat cohort study of untreated patients presenting with open-angle glaucoma or ocular hypertension. PARTICIPANTS: We included 30 treatment-naïve subjects. INTERVENTION: All subjects had 8 visits at which intraocular pressure (IOP) was measured by masked Goldmann tonometry. After the recruitment visit, IOP was measured in both eyes at 11 am for 7 consecutive weeks. At week 3, travaprost (0.001%) was commenced in the eye with the higher IOP and at week 4 travaprost was also commenced in the fellow eye. MAIN OUTCOME MEASURES: Three IOP outcomes were measured for the trial eye: (1) Unadjusted IOP-lowering effect (difference between recruitment IOP and first IOP on treatment); (2) adjusted IOP-lowering effect (unadjusted effect - [difference between IOPs at the same visits in the fellow eye]); and (3) true therapeutic effect (mean difference between 3 baseline pretreatment IOPs and 3 IOPs on treatment). RESULTS: Mean recruitment IOPs were 28.2 and 26.0 mmHg in the trial and fellow eyes, respectively. The mean baseline IOPs were 25.8 and 22.7 mmHg in the trial and fellow eyes, respectively, indicating that regression to the mean was responsible for 2.4 and 3.3 mmHg, respectively, in the trial and fellow eyes. The unadjusted treatment effect (11.7 mmHg) overestimated the true effect (8.6 mmHg) by a mean of 3.1 mmHg, whereas the mean adjusted IOP was almost identical to the true effect. The correlation between the unadjusted effect of treatment and the true effect was 0.55, whereas the effect when adjusted by the monocular trial was 0.72. CONCLUSIONS: In our cohort of patients with bilateral IOPs >21 mmHg at baseline, the monocular trial provides a significantly more accurate estimate of the therapeutic response when initiating prostaglandin monotherapy in untreated eyes. It is particularly helpful in avoiding overestimation of effectiveness and so reducing the number of patients on inadequate treatment. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any of the materials discussed in this article.

Treating patients presenting with advanced glaucoma--should we reconsider current practice?

The management of patients presenting with advanced glaucoma presents a challenge to glaucoma clinicians. Presentation with advanced visual field loss is an important risk factor for progression to blindness in the affected eye(s) during the patients' lifetime. Maximising intraocular pressure (IOP) control in such situations is likely to minimise the risk of further visual field deterioration thus either preventing or slowing progression to blindness. Currently most patients presenting with advanced disease in the UK are managed on an escalating regime of medical treatment. Should this fail glaucoma surgery is usually employed to further lower IOP. Although glaucoma surgery is generally a safe and successful intervention it carries a small risk of severe visual loss and is considered by many clinicians as an intervention only to be used following failure of medical treatment. Recently however the National Institute for Clinical Excellence has suggested in its clinical guidelines for management of ocular hypertension and glaucoma that primary surgery should be offered to patients presenting with advanced glaucomatous visual field loss. This is contrary to the practice of most UK ophthalmologists. In this review the current available evidence underlying the management of presentation with advanced disease is examined.

Outcome of repeat trabeculectomies.

BACKGROUND: To determine the success of repeat trabeculectomy augmented with mitomycin C in a cohort of patients who had undergone previously failed trabeculectomy surgery. DESIGN: A consecutive cohort series of patients. PARTICIPANTS: Fifty patients undergoing augmented trabeculectomy surgery following a previously failed trabeculectomy and at least 12 months' follow up. METHODS: All patients had demographic and clinical data collected at the time of surgery and at all subsequent follow-up visits. MAIN OUTCOME MEASURES: Visual field progression, loss of visual acuity, intraocular pressure (IOP) control. RESULTS: The mean follow up was 36.7 months. Forty-one patients (82%) achieved an IOP ≤21 mmHg (with ≥20% reduction of preoperative IOP) and ≥6 mmHg on no additional glaucoma treatment at 12 months' follow up. Forty-four patients (88%) achieved a qualified success with the same criteria at 1 year. The median logMAR acuity preoperative was unchanged after surgery; however, 11 patients (22%) lost ≥2 Snellen lines during follow up. There was no significant change in mean deviation during the follow-up period. CONCLUSIONS: Repeating trabeculectomy augmented with mitomycin C is an effective method of controlling IOP and preventing further visual deterioration in the majority of patients treated. However, visual loss was seen in a significant proportion of patients.

Moving the goal posts definitions of success after glaucoma surgery and their effect on reported outcome.

PURPOSE: To determine (1) the extent to which the definition of success of glaucoma surgery varies in the literature and (2) the degree to which the reported outcome after trabeculectomy is affected by the criteria used to define success. DESIGN: A systematic review of the literature and application of definitions to a retrospective cohort. PARTICIPANTS: A cohort of 100 patients who previously underwent trabeculectomy. METHODS: A literature search was performed of PubMed using the search term trabeculectomy for a 5-year period. Studies presenting original data relating to longitudinal intraocular pressure (IOP) control after glaucoma surgery were included. The definitions of success and failure used were documented for each publication. Each IOP-related definition of success was applied to a cohort of patients who previously underwent trabeculectomy. Success rates were derived for each published definition up to 36 months after surgery. MAIN OUTCOME MEASURES: Intraocular pressure measured by Goldmann applanation tonometry. RESULTS: From 100 publications meeting the inclusion criteria, 92 distinct IOP-related definitions of success were identified. Using these definitions, success rates for this series of 100 trabeculectomies varied between 36.0% and 98.0% after 3 years of follow-up. CONCLUSIONS: Over a recent 5-year period, there were nearly as many different definitions of success after glaucoma surgery as publications on the subject. The definition used markedly affects the quoted success rate after trabeculectomy, making interpretation of and comparison between published results extremely difficult. Standardization of published outcome parameters after glaucoma surgery is essential to allow meaningful comparisons between different study reports. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

24-Hour versus daytime intraocular pressure phasing in the management of patients with treated glaucoma.

AIMS: To determine the value of daytime and 24-h phasing in patients treated for progressive glaucoma despite apparently adequate intraocular pressure (IOP) control. METHODS: A retrospective analysis of a cohort of patients that had undergone either daytime phasing (08:00-18:00) or 24-h phasing was conducted. IOP measurements were compared between those taken in clinic, daytime phasing and 24-h phasing. The frequency with which phasing results changed clinical management was also compared between daytime and 24-h phasing. RESULTS: 76 patients fulfilling the study criteria were identified. Clinic and daytime phasing IOP were known for all 76 patients, nighttime IOP measurements were known for 41. There was no significant difference between mean IOP values measured in clinic and daytime phasing (p=0.062) or between clinic values and nighttime phasing (p=0.65). The mean daytime phasing IOP was significantly higher than the mean nighttime phasing IOP (p=0.038) (analysis of variance (ANOVA) for three groups, p=0.058). There was no significant difference between the mean peak IOP in clinic or daytime phasing (p=0.13) or between clinic and nighttime phasing (p=0.44). The mean daytime phasing IOP peak was significantly higher than the mean nighttime phasing IOP peak (p=0.015) (ANOVA for three groups, p=0.074). There was no significant difference in the frequency of a change in management that occurred as a result of phasing between the daytime and 24-h groups (p=0.65). CONCLUSIONS: 24-H phasing offers little advantage over daytime phasing in the identification of IOP fluctuations or peaks in patients progressing despite acceptable clinic IOP readings. Daytime phasing is likely to be more cost-effective than 24-h phasing.

Needling revision of trabeculectomies bleb morphology and long-term survival.

PURPOSE: To assess the long-term success rate and to determine factors that predict survival after 5-fluorouracil-augmented needling revision of poorly functioning trabeculectomy blebs. DESIGN: Prospective observational cohort study. PARTICIPANTS: Eighty-one consecutive patients undergoing bleb needling. METHODS: Survival analysis was performed after a minimum of 2 years' follow-up. Cox proportional hazards regression analysis was used to test the association between survival and study variables, including bleb morphology. MAIN OUTCOME MEASURES: Intraocular pressure (IOP) reduction by >20% and to 20% and to

Cataract surgery after needling revision of trabeculectomy blebs.

PURPOSE: To assess the effect of cataract surgery on trabeculectomy blebs that have previously had successful needling revision. STUDY DESIGN: A retrospective controlled study. PATIENTS AND METHODS: A cohort of patients undergoing needling of a poorly functioning trabeculectomy bleb was collected. From this cohort a group having had a successful needling outcome who subsequently underwent uneventful phacoemulsification was identified. Each member of this phacoemulsification group was matched with 2 controls from the cohort who had also had success from needling but who had not undergone cataract surgery. Survival analysis was performed using the date of cataract surgery as the entry time for the phacoemulsification group. For controls the entry time was the date of needling adjusted by subtracting the time between needling and cataract surgery of the matched phacoemulsification group subject. In this way an identical period had elapsed between needling and entry time for both phacoemulsification group and controls. Survival depended on (a) intraocular pressure (IOP) < or =21 mm Hg and (b) IOP <80% of preneedling IOP, on the same or fewer glaucoma drops and without further glaucoma surgery. RESULTS: Forty-five patients were included. Intervals from trabeculectomy to needling, needling to phacoemulsification, and from phacoemulsification to final follow-up ranged from 1 to 320, 4 to 15, and 5 to 19 months, respectively. Mean survival for the phacoemulsification group was 34.4 weeks and 190.0 for controls [hazard ratio 8.1 (95% confidence interval: 2.8-23.9) (log rank P<0.0001)]. Survival at final follow-up was 4/15 and 25/30 for cases and controls, respectively (chi2 P=0.0002). CONCLUSIONS: Previously successful bleb needling can be significantly compromised by subsequent cataract surgery.

Phaco-microtrabeculectomy: technique and intraocular pressure control in comparison with microtrabeculectomy.

PURPOSE: To describe a modified technique for combined cataract and glaucoma drainage surgery involving a small flap (micro) trabeculectomy combined with phaco-emulsification (PMT). To assess the level of intraocular pressure (IOP) control achieved by this procedure in comparison with microtrabeculectomy (MT) alone. METHODS: In this retrospective controlled case series records were reviewed for 37 consecutive low-risk patients undergoing PMT augmented with 5-fluorouracil (5-FU) and 37 low-risk subjects undergoing MT with 5-FU. IOP control was compared by survival analysis using IOP targets < or = 21 mmHg and < or = 16 mmHg at final follow up and with at least a 25% reduction from the preoperative pressure. RESULTS: Mean follow up was 41.7 months (range 19.0-72.0) in the PMT group and 43.5 months (range 18.0-66.0) in the MT group. A final IOP < or = 21 mmHg and with at least a 25% reduction from the preoperative pressure was achieved in 91.9% patients undergoing PMT (70.3% on no glaucoma drops). IOP < or = 16 mmHg and with at least a 25% reduction from the preoperative pressure was achieved in 67.6% (56.8% without drops). There were no significant differences in survival rates between PMT and MT for either IOP target. The mean final IOPs were 13.4 and 13.5 mmHg on a mean of 0.6 and 0.8 glaucoma drops in the PMT and MT groups, respectively. In the PMT final visual acuity improved by at least one Snellen line in 81.1% and was worse in a single eye. CONCLUSIONS: IOP control following combined surgery by PMT is as good as following MT alone.

Effect of diabetes mellitus and hyperglycemia on the proliferation of human Tenon's capsule fibroblasts: implications for wound healing after glaucoma drainage surgery.

Glaucoma drainage surgery in diabetic patients is associated with a relatively poor prognosis due to increased scarring at the site of surgery, secondary to increased proliferation of human Tenon's capsule fibroblasts (hTCF). This is in marked contrast to diabetic wound healing at other sites, where it is generally impaired. The aim of this study was to determine why diabetics show an increased ocular scarring response in comparison to that found at other sites. Under normoglycemic conditions, hTCF isolated from diabetics showed a mean reduction in short-term proliferation (95% CI) of 45 +/- 12% compared with normal controls (p < 0.001). Under hyperglycemic conditions, proliferation of diabetic hTCF was reduced by 21 +/- 11% (p < 0.01) compared with nondiabetic controls. When exposed to transforming growth factor-beta2 (1-10,000 pg/ml) and platelet-derived growth factor-BB (0.5-500 ng/ml) under both normo- and hyperglycemic conditions, there was a dose-related increase in proliferation of both diabetic and nondiabetic controls. There was no significant difference in response to cytokine stimulation between the two groups at any of the cytokine concentrations used. Western blot analysis did not show any apparent difference in the expression of platelet-derived growth factor receptor alpha, mitogen-activated protein kinase/ERK2, or transforming growth factor-beta receptor II to account for the reduced proliferation of diabetic hTCF. These results suggest that hTCF behave in a manner similar to fibroblasts from other nonocular sites and that the increased proliferation and scarring response found in vivo may be secondary to the previously noted elevated cytokine concentrations in the aqueous and vitreous of diabetics.