Scleral contact lenses for overnight wear in the management of ocular surface disorders.

PURPOSE: To describe the use of overnight wear scleral contact lenses (Scl CLs). The authors describe 7 patients using this modality of contact lens wear. Most of the lenses were made from highly gas-permeable materials, but a long-standing case is also reported when the lenses were made from PMMA, which is impermeable to gases. BACKGROUND: There is a range of therapeutic indications for the use of Scl CLs. The development of rigid gas-permeable (RGP) materials has widened this range. CASE REPORTS: Seven case reports are presented which describe patients in whom severe ocular surface disease has been managed with overnight-wear Scl CLs. The indications were: corneal exposure, post-radiotherapy complications, Stevens Johnson disease, recurrent erosion and congenital or post-surgical lid defects. CONCLUSION: Scl CLs provide a therapeutic option for a range of complicated corneal and ocular surface conditions for which the treatment by other methods is either unsuitable or less effective. They have several advantages over silicone rubber and hydrogel lenses. The relative ease of handling for some patients allows removal for cleaning, their rigidity gives stability and a high degree of protection to the ocular surface, and the presence of a pre-corneal fluid reservoir optically neutralises an irregular corneal surface. Highly oxygen-permeable materials enable consideration of overnight wear in appropriate circumstances.

Factors leading to lens implant decentration and exchange.

PURPOSE: To examine the intra- and post-operative factors leading to posterior chamber intraocular lens (IOL) decentration in patients requiring IOL exchange, and to identify avoidable causes of IOL decentration. METHODS: Case records of 17 patients who had undergone posterior chamber IOL exchange were examined for: (i) any complication or alteration to the original intended surgical procedure, (ii) IOL type and position at the completion of initial surgery, (iii) IOL position at the time of re-operation. RESULTS: The decentred lens implants were injected silicone plate-haptic IOLs in 10 patients, small (5.5 mm) optic diameter PMMA IOLs in 4 patients and large (7 mm) optic diameter PMMA IOLs in 3 patients. In all cases, decentration was due to IOL subluxation. Early decentration of the injected lenses was due to IOL implantation in eyes without a continuous capsulorrhexis. In contrast late decentration was due to subluxation associated with capsule fibrosis. Decentration of small optic PMMA IOLs was found to be associated with an anterior capsule tear and haptic malposition in the ciliary sulcus. Decentration of large optic PMMA IOLs was associated with posterior displacement of one haptic through a posterior capsule defect, zonule dehiscence or fixation of one haptic in the sulcus and one in the capsule bag. CONCLUSION: Clinically significant post-operative subluxation of injected silicone IOLs may be minimised by implanting only into a lens capsule bag with an intact capsulorrhexis. The risk of decentration of small optic PMMA IOLs may be minimised by positioning the haptics at 90 degrees to any capsulorrhexis tear. After cataract surgery complicated by posterior capsule rupture or zonule dehiscence, it is important to assess the remaining capsule support and, where sufficient, implant a large optic diameter posterior chamber IOL in the ciliary sulcus.

Per-operative retinoscopy as a predictor of final post-operative refraction.

PURPOSE: To assess the accuracy of streak retinoscopy performed at the end of cataract surgery as a predictor of final post-operative error. METHOD: Retinoscopy was performed on 68 patients as they lay on the operating table after routine cataract extraction and intraocular lens implantation. In each case the predicted post-operative refraction by biometry and the retinoscopy at the end of the operation were compared with the 6 week post-operative subjective refraction. RESULTS: The retinoscopy had a mean difference of 0.6 D (standard deviation of 0.5 D). The post-operative refraction predicted by biometric measurements had a mean difference of 1.6 D (standard deviation 0.6 D). When corrected for systematic error, 8% of patients were found to have an error of greater than 2 D as predicted by pre-operative biometry. Prediction by retinoscopy made no error greater than 2 D. The accuracy in the retinoscopic prediction of post-operative refraction was significantly better than the biometry using the F-test (p = 0.001). CONCLUSION: Retinoscopy at the end of cataract surgery may be a valuable tool to alert the surgeon to an unexpected refractive error. This would enable immediate intraocular lens exchange, if required.

The solution structure of human transforming growth factor alpha.

The solution structure of transforming growth factor alpha has been determined by a combination of high-resolution 1H-nuclear magnetic resonance and distance geometry and restrained molecular dynamics. The 382 restraints derived from the NMR experiments were used to calculate many distance geometry structures, which were then refined by restrained molecular mechanics. Five of these structures were further refined using a variety of methods. Comparison of independently measured parameters, such as calculated hydrogen bonding patterns and experimental amide exchange rates, have been used to evaluate the accuracy of the structures. Also, possible mechanisms to explain the pH-dependent conformational interconversion observed are suggested. Finally comparisons between this work and others on this topic have been made.

Nuclear-magnetic-resonance studies of human epidermal growth factor.

The 1H-NMR spectra of native human epidermal growth factor (EGF) and a derivative lacking the final five residues have been assigned by two-dimensional methods, enabling their structures to be compared. The same structural features are observed for each protein, although the final five residues of native human EGF interact with residues earlier in the sequence. Comparison of the resonance shifts of human, rat and mouse EGF and human transforming growth factor alpha (TGF alpha) enables shifts characteristic of the EGF conformation to be identified, providing standards by which the structures of related proteins may be assessed.

Structure-function relationships in epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha).

The solution structures of the homologous growth factors human epidermal growth factor (hEGF) and human transforming growth factor-alpha (hTGF-alpha), as determined by high resolution NMR and various computational methods, are described. Knowledge of these structures and the sequences of other homologous proteins leads to predictions about growth factor residues which may be involved in the receptor/ligand interface. Recent experiments designed to check these predictions are described briefly. These involve site-specific mutagenesis, receptor binding assays and high resolution NMR studies.

A high-resolution 1H-NMR study of human transforming growth factor alpha. Structure and pH-dependent conformational interconversion.

The 500-MHz and 600-MHz 1H-NMR spectra of recombinant human transforming growth factor alpha have been recorded at pH values of 3.8, 6.5 and 9.4. Analysis of various two-dimensional spectra has enabled sequence-specific assignments to be made and the secondary structure to be identified. Information on the tertiary fold has also been obtained from observed nuclear Overhauser effects and titration of histidine residues. The overall fold of the protein is very similar to that of epidermal growth factor, as might be expected from the sequence similarity. However, the structure of transforming growth factor alpha at pH 3.8 is found to show interesting differences from those at the two higher pHs and from that of epidermal growth factor.

The solution structures of epidermal growth factor and transforming growth factor alpha.

The structures of human epidermal growth factor (EGF) and human transforming growth factor alpha (TGF alpha) have been determined in solution using nuclear magnetic resonance techniques. The features of each structure are described and similarities and differences between them are discussed. The structures are combined with information from sequence homologies to produce a model of the receptor-recognition sites of EGF and TGF alpha, which can be tested in a site-directed mutagenesis programme. The model assists in explaining previous observations of sequence-activity relationships. The TGF alpha and EGF structures also serve as models for homologous modules in other extracellular proteins.

The structure of melittin. A 1H-NMR study in methanol.

The conformation of the 26-residue polypeptide melittin has been studied using 1H-NMR spectroscopy in methanolic solution. The 1H-NMR spectrum of melittin has been assigned using two-dimensional NMR techniques and the secondary structure has been calculated from nuclear Overhauser enhancement data using distance geometry and restrained molecular dynamics analyses. The structure is found to be mainly helical, and similar to that found in crystals from diffraction data: residues 2-11 and 13-26 form regular alpha-helices joined by a 'hinge' between residues 11-12. The structure in this hinge region is shown to be significantly different from that in the crystal structure, leading to a smaller angle between the two helices. The possible significance of the proline residues in this and similar membrane-spanning peptides is discussed.

High-resolution 1H NMR study of the solution structure of delta-hemolysin.

The 26-residue toxin from Staphylococcus aureus, delta-hemolysin, is thought to act by traversing the plasma membrane. The structure of this peptide, in methanol solution, has been investigated by using high-resolution NMR in combination with molecular dynamics calculations. The 1H NMR spectrum has been completely assigned, and it is shown that residues 2-20 form a relatively stable helix while the residues at the C-terminal end appear to be more flexible. The structures were calculated only from nuclear Overhauser effect data and standard bond lengths. It is shown that the results are consistent with 3JNH-alpha CH coupling constants and amide hydrogen exchange rates.

The solution structure of human epidermal growth factor.

The epidermal growth factors (EGFs) are powerful mitogens for a wide variety of cells in culture; human EGF (hEGF), known as urogastrone, also inhibits gastric acid secretion in vivo. The transforming growth factors (TGF-alpha) are related to the EGF family both in sequence and activity and EGF-like sequences are often observed in a wide range of functionally unrelated proteins. Attempts to examine the structure of EGF by diffraction methods have not yet succeeded because of difficulties with crystallization. We report here a three-dimensional structure of a biologically active derivative (residues 1-48) of the 53-residue human EGF. An analysis of high resolution 1H nuclear magnetic resonance (NMR) spectra was used together with a combination of distance geometry, restrained energy minimization and restrained molecular dynamics methods. The three-dimensional structure provides a basis for understanding the properties of EGFs and for predicting the structures of homologous sequences in other proteins.