Comparison of Luneau SA disposable and Goldmann applanation tonometer readings.

PURPOSE: To test the agreement of intraocular pressure (IOP) measurements made with Luneau SA applanators and Goldmann applanator. MATERIALS AND METHODS: A single-blind crossover trial. IOPs were measured in both eyes of subjects with both applanators. Type of applanator was alternated to eliminate systematic bias. Multiple observers were used. Observers were blind to the scale while performing measurements but not to the type of applanator used. The appearance of the meniscus was assessed semiquantitatively. All measurements were combined and presented in a Bland-Altman plot. RESULTS: A total of 140 eyes of 79 subjects were tested by seven observers. The range of measurements was 6-45 mmHg (mean 17.8 mmHg) for the Goldmann applanator. On average, the Luneau SA applanator (range of measurements 4-36 mmHg) gave a measurement of 2.35 mmHg less than the Goldmann standard. The standard deviation of these differences was 2.13 mmHg, giving an upper 95% confidence limit of 6.53 mmHg and a lower 95% confidence limit of -1.83 mmHg. The measurements agreed in only 24 out of 140 instances. In 28 eyes, the disposable tonometer end point was difficult to assess owing to excessively thick rings. Linear extrapolation suggests an increase in difference with increasing IOP. CONCLUSION: The inter-head inaccuracy, tendency to underestimate IOP, and lack of systematic inaccuracy make a corrective algorithm impossible to formulate. The range of variation between the Luneau SA disposable applanator and the Goldmann standard is sufficiently large to influence clinical management decisions. We speculate that one explanation is the interaction of the tonometer with the tear film, making end point determination difficult. Further research is being undertaken.

Agaricus bisporus (edible mushroom lectin) inhibits ocular fibroblast proliferation and collagen lattice contraction.

The edible mushroom lectin from Agaricus bisporus (ABL) has antiproliferative effects on a range of cell types. This investigation was undertaken to test whether it might have inhibitory activity on Tenon's capsule fibroblasts in in vitro models of wound healing and therefore have a use in the modification of scar formation after glaucoma surgery.Human ocular fibroblasts in monolayers and in three-dimensional collagen lattices were exposed to ABL (0-100 microg ml(-1)). Proliferation was studied by the MTS assay and by counting haematoxylin-stained cells; contraction was measured as a change in the diameter of three-dimensional collagen lattices. Toxicity was investigated using a fluorescent viability assay. FITC-labelled lectin was used to study cell binding and internalization of ABL.ABL caused a dose-dependent inhibition of proliferation and lattice contraction without significant toxicity. Proliferation was inhibited by 5-40% in the dose range 20-100 microg ml(-1) Significant inhibition of lattice contraction was achieved with 40 microg ml(-1) ABL, and at 100 microg ml(-1) contraction was completely prevented. FITC-ABL binds to the cell surface and accumulates around the nuclear envelope when internalized. These experiments have shown that ABL possesses key features required of an agent that might control scarring processes and suggest that ABL might be especially useful where subtle modification of healing is needed. Further evaluation is warranted.

Collagen corneal shields.

Collagen corneal shields were developed as a corneal bandage lens and are currently indicated for ocular surface protection following surgery and in traumatic and nontraumatic corneal conditions. Collagen shields are manufactured from porcine or bovine collagen and three different collagen shields are currently available with dissolution times of 12, 24, and 72 hours. The theoretical, experimental, and clinical evidence supports a role for collagen corneal shields as a drug delivery device and in the promotion of epithelial and stromal healing. Presoaking the collagen shield in a pharmacological agent with adjunctive topical treatment represents the most efficacious method of utilizing collagen shields for drug delivery. In microbial keratitis collagen shields can enhance drug delivery, promote epithelial and stromal healing, neutralize collagenases, and reduce corneal inflammation. This review will examine the evidence that supports the role of collagen shields in drug delivery and corneal wound healing. Despite a large volume of experimental (animal) work, studies on human subjects, particularly randomized controlled trials, are lacking. The authors are advocating the reassessment of the application and benefits of corneal collagen shields to clinical practice.

Endoscopic-guided trephination dacryocystorhinostomy (Hesham DCR): technique and pilot trial.

OBJECTIVES: (1) Test the feasibility and the safety of guided transnasal trephination in creating a nasolacrimal fistula. (2) Develop an appropriate lacrimal maintainer and test its value in modulating healing at the fistula site. DESIGN: Prospective, noncomparative interventional case series. PARTICIPANTS: Five cadavers and 19 patients. METHOD: A transcanalicular lacrimal probe penetrated the lacrimal fossa to guide the passage of a flexible trephine up the nose, which created the nasolacrimal communication. A special wide-caliber lacrimal maintainer was inserted along lacrimal tubes within the created passage. OUTCOME MEASURES: For cadaveric study, direct inspection after dissection of the facial flap was performed. For the clinical trial, subjective improvement in watery eye, dye testing, lacrimal probing, lacrimal irrigation, and endoscopic nasal examination. RESULTS: The technique resulted in the creation of a regular fistula of reproducible diameter into which a standard-shaped wide caliber maintainer could be inserted. Three months after removal of the maintainer and 6 months after surgery, a patent ostium was achieved in 17 of 18 (94%) patients who had a completed procedure. Relief of symptoms was achieved in 83%. CONCLUSIONS: Guided endoscopic dacryocystorhinostomy provides a simple and safe option for the treatment of nasolacrimal duct obstruction. The lacrimal maintainer is a useful device to achieve a large patent nasolacrimal communication.

Missense mutations in COL8A2, the gene encoding the alpha2 chain of type VIII collagen, cause two forms of corneal endothelial dystrophy.

Corneal clarity is maintained by its endothelium, which functions abnormally in the endothelial dystrophies, leading to corneal opacification. This group of conditions includes Fuchs' endothelial dystrophy of the cornea (FECD), one of the commonest indications for corneal transplantation performed in developed countries, posterior polymorphous dystrophy (PPCD) and the congenital hereditary endothelial dystrophies (CHED). A genome-wide search of a three-generation family with early-onset FECD demonstrated significant linkage with D1S2830 (Z(max) = 3.72, theta = 0.0). Refinement of the critical region defined a 6-7 cM interval of chromosome 1p34.3-p32 within which lies the COL8A2 gene. This encodes the 703 amino acid alpha2 chain of type VIII collagen, a short-chain collagen which is a component of endothelial basement membranes and which represented a strong candidate gene. Analysis of its coding sequence defined a missense mutation (gln455lys) within the triple helical domain of the protein in this family. Mutation analysis in patients with FECD and PPCD demonstrated further missense substitutions in familial and sporadic cases of FECD as well as in a single family with PPCD. This is the first description of the molecular basis of any of the corneal endothelial dystrophies or of mutations in type VIII collagen in association with human disease. This suggests that the underlying pathogenesis of FECD and PPCD may be related to disturbance of the role of type VIII collagen in influencing the terminal differentiation of the neural crest derived corneal endothelial cell.

Agreement between ophthalmologists and optometrists in optic disc assessment: training implications for glaucoma co-management.

BACKGROUND: Many studies have estimated observer variability for optic disc assessment among experts, but there are few data on agreement between optometrists and ophthalmologists. The aim of this study is to report inter- and intraobserver agreement among optometrists and ophthalmologists in optic disc assessment and discuss the implications for glaucoma co-management. METHODS: Twelve observers (six optometrists and six ophthalmologists) graded 48 stereo-pairs of optic disc photographs from 48 patients on two separate occasions. Observers graded the vertical C/D ratio, the narrowest rim width and the presence/absence of disc haemorrhage. Agreement was assessed by calculating the standard deviation (SD) of differences and the kappa statistic, within and between observers. Systematic differences in grading between and within individuals were described by calculating mean differences. RESULTS: Intra-observer agreement is "substantial" and significantly better than inter-observer agreement for all disc features (P<0.0001). Intra-observer agreement is comparable for optometrists and ophthalmologists with regard to C/D ratio estimates. Although some optometrists show close agreement with ophthalmologists, overall agreement between optometrists and ophthalmologists is significantly worse than agreement among ophthalmologists alone for vertical C/D ratio (P=0.002) and disc haemorrhage (P=0.02). There are fewer inter-observer mean differences that differ significantly from zero among ophthalmologists (7%) than among optometrists (67%; chi2=11.63, P<0.001) or between optometrists and ophthalmologists (69%; chi2=16.7, P<0.001). There is evidence of systematic under-reading of C/D ratios by less experienced optometrists. CONCLUSION: Although individual optometrists can show good agreement with ophthalmologists on disc grading, the variation in individual performance indicates that training and accreditation in disc assessment is an essential prerequisite for participation by optometrists in glaucoma co-management.

Endonasal laser dacryocystorhinostomy and external dacryocystorhinostomy outcome profile in a general ophthalmic service unit: a comparative retrospective study.

PURPOSE: To evaluate the outcome profile of endonasal laser dacryocystorhinostomy (ENL-DCR) in comparison with external dacryocystorhinostomy (ENL-DCR) carried out as part of general ophthalmic service within the same center. METHODS: Patients who have undergone external or endonasal laser DCR in the authors institute with a minimum follow-up of 9 months and at least 3 months after removal of the tubes were invited to participate in this research. We used a questionnaire and a systematic clinical examination for detecting lacrimal passage patency and function. Patients were classified into categories: complete anatomical and physiological success; anatomical success with partial relief of symptoms; anatomical success with no relief of symptoms; anatomical failure. The endoscopic view of the ostium vertical location has been classified into four levels. RESULTS: One hundred and ten external-DCR and 53 Endonasal-DCR procedures were evaluated. Free communication (anatomical success) was achieved in 82% undergoing Ext-DCR and in 58% undergoing ENL-DCR. A significant number of patients continued to have symptoms in spite of a patent fistula (54% for Ext-DCR and 39% for ENL-DCR). The site of the opening of the internal ostium was significantly related to the persistence of symptoms in spite of free communication (P < 0.001, chi-square test). CONCLUSION: In this series of patients undergoing DCR in a general ophthalmic unit, the standard Ext-DCR technique has a higher anatomical success rate than the endoscopic laser DCR but not necessarily with equivalent rate of relief of symptoms. An inferiorly placed ostium is more likely to result in complete relief of symptoms.

Intraocular pressure and pulse rate measurements by the OBF tonograph--comparison to reference instruments.

The purpose of this study was to evaluate the accuracy of intraocular pressure (IOP) and ocular pulse rate (OPR) measurements obtained by the Ocular Blood Flow (OBF) tonograph (OBF Labs, Wiltshire, UK). Measurements of IOP and OPR by the OBF tonograph were compared to those of reference instruments. For IOP evaluation, measurements were obtained on patients with normal and abnormal pressures using the OBF tonograph and the Goldmann applannation tonometer in random alternate order. For the OPR evaluation, measurements were obtained using the OBF tonograph with simultaneous heart rate monitoring by ECG on patients with normal IOP. The validity of the OBF tonograph measurements was quantified in terms of 95% limits of agreement and their relationships to measurements by reference instruments was determined by linear regression analyses. 102 patients were recruited for IOP measurements. Mean IOP obtained by the Goldmann tonometer was 20.7 mmHg (7-42 mmHg, SD 6.98) whilst mean IOP obtained by the OBF tonograph was 20.1 mmHg (8.1-40.2, SD 6.1). Goldmann IOP and OBF tonograph IOP readings were well correlated (r = 0.945). Analysis of the difference in IOP measurements between two instruments (tonograph minus Goldmann tonometer) showed the mean bias to be 0.26 mmHg (-7.8 to +6.1 mmHg) and the 95% limits of agreement to be -4.35 to +4.87 mmHg. Agreement between two instruments appeared to be dependent on the IOP; at IOP lower than 20.6 mmHg there was an overall tendency for the tonograph IOP to be higher than Goldmann IOP and vice versa when IOP was above 20.6 mmHg. 47 patients were recruited for OPR and ECG measurements. Mean pulse rates were 74.8 beats per min (mean 43-110) by ECG and 73.9 beats per min (43-110) by tonography. Analysis of the difference in pulse rate between instruments (tonograph OPR minus ECG pulse rate) against the average pulse rate showed the mean bias to be -0.8 beats and the 95% limits of agreement to be between -7 to +5 beats. Ocular pulse rate values obtained by the OBF tonograph were very accurate when compared to ECG pulse rate. This indicates that there is unlikely to be a systematic lag in continuous ocular pulse waveform recording. Intraocular pressure measurements by the OBF tonograph correlated very well with Goldmann readings over a wide range of pressures and should be valid in the clinical setting.

Aqueous humor stimulates the migration of human trabecular meshwork cells in vitro.

PURPOSE: Depletion of trabecular meshwork cell numbers is a feature of the outflow system in aging and in primary open-angle glaucoma. It is possible that migration stimulated by factors present in aqueous humor may contribute to the cell loss. This investigation assessed the chemoattractant potential of glaucomatous and nonglaucomatous human aqueous humor and fibronectin, one of its constituents, on a range of cultured trabecular meshwork cell lines. METHODS: Migration was assessed in 48-well modified Boyden chambers. The potential migratory stimulants were soluble fibronectin and glaucomatous and nonglaucomatous aqueous humor. The glaucomatous aqueous samples were collected from patients undergoing trabeculotomy for primary open-angle glaucoma and the normal aqueous from normal bovine eyes and patients undergoing cataract surgery. The target cell types were normal human and bovine meshwork cells grown from explants and two human transformed meshwork cell lines from a normal (HTM-5) and a glaucomatous (HTM-3) source. RESULTS: Soluble fibronectin stimulated all the target cells to migrate with an optimal concentration ranging from 1 to 30 microg/ml, and Zigmond Hirsch checkerboard analysis indicated that both chemotaxis and chemokinesis took place. All the aqueous humor samples stimulated migration of the meshwork cell lines at an optimal concentration of 200 microl/ml. Glaucomatous aqueous humor stimulated a greater migratory response than nonglaucomatous aqueous for two of the four target cell types (P < or = 0.03). Neutralization of the fibronectin content of nonglaucomatous and glaucomatous aqueous by addition of excess anti-fibronectin antibody indicated that fibronectin could account for 35% to 80% of the migratory activity of the aqueous. CONCLUSIONS: Aqueous humor contains potentially powerful chemoattractants for trabecular meshwork cells. The activity of one of these constituents, fibronectin, has been accounted for by this study. Glaucomatous aqueous appears to be as good and in some cases a better migratory stimulant than nonglaucomatous aqueous in vitro. The migratory evidence points to a trend that may help to explain cell loss in the aging meshwork and possibly some of the extra loss in primary open-angle glaucoma.

Modulation of retinal pigment epithelial cell behavior by Agaricus bisporus lectin.

PURPOSE: To determine whether Agaricus bisporus lectin (ABL) binds retinal pigment epithelial cells (RPEs), to conduct a preliminary viability study of RPEs exposed to ABL, and to evaluate the effects of ABL on RPE proliferation and RPE-mediated matrix contraction in vitro. METHODS: Using cultured bovine RPEs, immunohistochemistry was used to study ABL binding. Morphologic and trypan blue exclusion techniques were used for toxicity studies. The effect of ABL on RPE proliferation was investigated by [methyl-3H]-thymidine incorporation. The effect of ABL on RPE-mediated matrix contraction was evaluated with RPE-populated three-dimensional collagen matrices. RESULTS: ABL bound to RPE cells. This binding was inhibited by asialomucin. No change in RPE morphology or trypan blue exclusion compared with controls was observed in RPEs incubated with 5 to 60 microg/ml ABL for 3 days. Twenty-four-hour incubations of RPEs with ABL significantly inhibited RPE proliferation in a dose-dependent way, 40 microg/ml ABL inhibited proliferation by 83% (SE 14, P<0.05). ABL showed a dose-dependent significant inhibition of RPE-mediated collagen matrix contraction over 3 days, with 93% inhibition compared with controls by 40 microg/ml lectin (P<0.05). The inhibitory effect of ABL on proliferation and gel contraction was partly reversible after eliminating ABL from the culture medium. CONCLUSIONS: Bovine RPE cells bind ABL, and preliminary evaluations suggest that levels of ABL that are nontoxic to the cells potently inhibit RPE proliferation and RPE-mediated matrix contraction. ABL deserves further investigation as a potential inhibitor of RPE proliferation and cell-mediated matrix contraction in anomalous reparative processes such as proliferative vitreoretinopathy and as a laboratory tool for RPE behavioral studies.

Repair in avascular tissues: fibrosis in the transparent structures of the eye and thrombospondin 1.

Wound repair is a process which is normally dependent on the vasculature of the damaged tissue. However, the transparent structures of the eye (e.g. central cornea, lens, vitreous) are avascular and yet are still subject to repair and fibrosis. Moreover, the resulting ophthalmic scars often remain avascular. Since this type of ocular scarring may result in blindness, it is the subject of intense research. An aspect of avascular ophthalmic fibrosis which has attracted attention is the question concerning early wound healing components that are usually derived from blood constituents. One such molecule is the glycoprotein thrombospondin 1. Thrombospondin 1 is thought to be a key regulator of cell behaviour in early wound repair and appears to be derived totally from platelet alpha-granules during repair of incisional skin wounds. It has been shown that the ocular cells involved in avascular repair processes, and which are thus responsible for healing in the absence of platelet-derived thrombospondin 1, are capable of synthesizing the protein themselves. It is suggested that cells involved in ophthalmic repair processes produce thrombospondin 1 in the absence of the platelet-derived molecule. Local synthesis of thrombospondin 1 may represent a therapeutic target in the management of ophthalmic fibrosis.

Pulsatile ocular blood flow measurements in healthy eyes: reproducibility and reference values.

PURPOSE: To determine the reproducibility and the normal reference range of pulsatile ocular blood flow (POBF) values in healthy subjects using the Ocular Blood Flow Tonograph (OBF Laboratories, UK Ltd., Wiltshire, England). METHOD: Pulsatile ocular blood flow was measured in one eye of each of 83 patients. Coefficient of reliability was determined by calculation of intraclass correlation coefficient via one-way analysis of variance. Mean difference between measurements was calculated for bias and first exposure effects. Pulsatile ocular blood flow from 163 healthy individuals were analyzed to determine the distribution, mean, standard deviation (SD), range, and the 5th and 95th percentile values. The influence of age, blood pressure, pulse rate, and intraocular pressure on pulsatile ocular blood flow was determined by regression analysis. RESULTS: Reliability coefficient for pulsatile ocular blood flow values ranging from 290 microliters/min to 2,196 microliters/min was 0.92. Variation in bias and first exposure effect were not significant. Pulsatile ocular blood flow values were normally distributed. Mean values were 669.90 +/- 233.0 microliters/min in men and 841.90 +/- 254.6 microliters/min in women. Fifth and ninety-fifth percentile values were 364.75 microliters/min and 1,266.10 microliters/min in men and 397.18 microliters/min and 1,346.10 microliters/min in women. Pulsatile ocular blood flow was significantly influenced by pulse rate. CONCLUSION: This study confirms the reliability of the Ocular Blood Flow Tonograph in repeated measurements of POBF within individuals over short time intervals. The high interindividual variation in POBF may invalidate comparison of POBF between individuals, and the wide range of normal values may limit the value of using a low POBF as a possible indicator of disease.

Inter-observer agreement in clinical optic disc measurement using a modified 60 D lens.

PURPOSE: To assess the inter-observer agreement of the measurement of optic disc dimensions by two observers using a modified 60 dioptre (D) fundus examination lens. METHOD: The vertical disc and cup diameters of 29 eyes were measured by two independent observers using a 60 D lens modified by incorporation of a 0.1 millimetre scale graticule. The vertical cup/disc ratio was calculated. Inter-observer agreement was assessed by calculation of the inter-observer differences and by the weighted kappa statistic. RESULTS: The two observers showed good agreement for the measurement of disc diameter (mean difference -0.04; range -0.04, 0.2) and for cup diameter (mean difference -0.03; range 0.3, 0.2). Closer agreement for the vertical cup/disc ratio was achieved (mean kappa 0.96; 95% confidence limits 0.90, 1.0). The 95% confidence limit for the mean inter-observer difference in cup/disc ratio was 0.11, suggesting that a change of > 0.1 in the assessment of the cup/disc ratio by this technique is significant at the 5% level. CONCLUSION: High inter-observer agreement of optic disc measurement can be achieved with this technique. The method has the potential to improve the clinical evaluation of the optic disc and the precision and accuracy of the clinical measurement of other fundal structures.

Ophthalmic complications of HIV/AIDS.

As a result of improved treatment and patient survival, ophthalmic complications are now being seen with increasing frequency in AIDS, occurring in up to 75% of patients during the course of the disease. The eye may be involved by an AIDS-related microvasculopathy, which gives rise to cotton wool spots, and by opportunistic infections caused by a wide range of organisms, including cytomegalovirus, herpes simplex virus, varicella zoster, Toxoplasma gondii, Mycobacterium avium-intracellulare, Treponema pallidum, Pneumocystis carinii and various fungal agents. Opportunistic infections may be the presenting sign of disseminated infection. The eye may also be involved by neoplasms such as Kaposi's sarcoma and lymphoma, and by intracranial disease. Ocular involvement may lead to blindness if untreated and prompt ophthalmological referral is essential. This article reviews the range of ocular diseases seen in HIV and AIDS, current therapeutic options and outcome.