Lydia Chang

Trabeculectomy, risk factors for failure and the preoperative state of the conjunctiva.

Trabeculectomy remains the gold-standard surgical method for reduction of intraocular pressure (IOP) in the management of glaucoma. Reported success rates for trabeculectomy vary enormously, but the success rate is considered reasonable in most eyes. However, trabeculectomy cannot yet be performed with a virtual guarantee of success in all glaucomatous eyes. For this reason, research continues in an attempt to refine the procedure. Failure of trabeculectomy is most frequently the result of subconjunctival fibrosis (bleb failure) as the postoperative wound healing process proceeds to an extent greater than desired. When bleb failure occurs, which tends to be in the early postoperative months, there is a hypercellular response characterized by inflammation and fibroblast proliferation, migration, and extracellular matrix deposition (wound healing). A number of risk factors for failure of trabeculectomy have been identified, and a variety of methods have been proposed to improve the results in eyes considered at particular risk. Currently, the most popular method used to enhance trabeculectomy function is chemical inhibition of wound healing localized to the site of surgery. Topical steroids have been used to limit the wound healing process since trabeculectomy was first described, but more potent wound healing inhibition has come to play a more significant role in recent years. Initial use of adjunctive antifibrotic agents was based on the premise that excessive wound healing involved the proliferation of cells, mainly fibroblasts, and that inhibition of this process would limit the healing at the site of the fistulizing surgery. Both 5-fluorouracil (5-FU) and mitomycin-C (MMC) now have important roles in the treatment of certain patients undergoing surgical therapy for glaucoma by inhibition of fibroblastic proliferation and limiting the postoperative scarring response. Unfortunately, potent antifibrotic agents such as 5-FU and MMC, although they aid the IOP-lowering effect, can be associated with significant adverse side effects and complications. Research continues to develop more physiologic mediators to modulate postoperative wound healing with greater predictability of effect and increased safety from adverse events. This article takes a step back to review the research that has been carried out in investigating the preoperative state of the conjunctiva before performing trabeculectomy. The article addresses two perspectives: first, the clinical risk factors for filtration failure and second, possible perioperative conjunctival cellular mechanisms underlying the risk factors. The preoperative state of the conjunctiva, which acts as a reservoir for fibroblast recruitment at the site of filtration surgery, is likely to play a crucial role in the behavior of the tissue in its response to the trauma of surgery. Perhaps of more importance, the relationship between the conjunctival cellular profile and risk factors for failure of trabeculectomy identified before surgery will be critical in the development of targeted, patientspecific, wound healing modulators.

Modulation of wound healing after glaucoma surgery.

The healing process after glaucoma filtration is the main determinant of surgical failure and, even more important, the final intraocular pressure. The ability to fully control wound healing may ultimately give us the ability to set the intraocular pressure in the low teens for all patients undergoing glaucoma filtration surgery. The authors review the changes in how to use antimetabolites to improve safety, and many of the exciting new areas of progress, including growth factor neutralization and future molecular therapies to control wound healing.

The Role of the Immune System in Conjunctival Wound Healing After Glaucoma Surgery

The immune system has a fundamental role in the development and regulation of ocular healing, which plays an important role in the pathogenesis of most blinding diseases. This review discusses the mechanisms of normal wound healing, describing the animal and fetal wound healing models used to provide further insight into normal wound repair. In particular, conjunctival wound repair after glaucoma filtration surgery will be used to illustrate the contributions that the different components of the immune system make to the healing process. The potential role of macrophages, the possible regulatory effect of lymphocytes, and the important role of growth factors and cytokines in the wound healing reaction are discussed. The significance of the immune system in the pathogenesis of aggressive conjunctival scarring is addressed, particularly assessing the predisposing factors, including drugs, age, and ethnicity. The rationale behind the pharmacological agents currently used to modulate the wound healing response and the effects these drugs have on the function of the immune system are described. Finally, potential new therapeutic approaches to regulating the wound healing response are reported.

Modulating conjunctival wound healing

Advances in molecular and cell biology have led to an expansion in our knowledge and understanding of the processes involved in wound healing. We review existing and potential therapies modulating the conjunctival scarring response, with particular reference to glaucoma filtration surgery. We discuss how the refinement of present antimetabolite regimens can minimise complications and improve surgical results, and advocate their use in carefully selected patient groups. Perhaps the most promising approach is targeting biological molecules. Hence, use of fully human neutralising monoclonal antibodies to the growth factor TGFfβ has potential as a useful strategy for modifying conjunctival scarring. Combination therapies may also afford an improved therapeutic index. It is hoped that future therapies can offer safer, more specific, focal and titratable treatment, with far-reaching clinical applications.

Can a community optometrist-based referral refinement scheme reduce false-positive glaucoma hospital referrals without compromising quality of care? The community and hospital allied network glaucoma evaluation scheme (CHANGES)

Background/AimsTo describe the design, activity, and quality of the referral refinement phase of a novel glaucoma shared-care scheme.MethodsEight Optometrists with a Specialist Interest in glaucoma (OSI) were trained to perform a community-based comprehensive glaucoma evaluation of low-risk glaucoma hospital referrals (only one/none of the following factors noted for either eye: abnormal optic disc, abnormal visual field, abnormal intraocular pressure (IOP; 22–28 mmHg or IOP asymmetry)) using equipment standardized to that of the hospital glaucoma service.ResultsOne hundred and thirty-eight (27%) of a total of 512 glaucoma-related referrals were deemed ‘low risk’. Their choice of OSI discharged 40 (35%). The consultant agreed (virtually) with the decision to discharge with 28 (70%) and disagreed with 12 (30%). Comparing findings between OSI and consultant for 99 referred patients, sensitivity, specificity, and negative predictive values for a suspicious optic disc were 78, 61, and 79%, respectively. For an IOP of >21 mmHg, they were 74, 85, and 90%, respectively. For an occludable anterior chamber angle (Van Hericks versus gonioscopy), they were 69, 88, and 94%, respectively.ConclusionThis referral refinement process can reduce numbers of false-positive referrals attending the hospital glaucoma service while retaining a relatively high level of examination quality.

Intraocular pressure outcome in primary 5FU phacotrabeculectomies compared with 5FU trabeculectomies.

PurposeCombined surgery for glaucoma and cataract may not achieve as low intraocular pressure (IOP) as compared with trabeculectomy alone. The aim of this study was to assess the IOP control of 5-fluorouracil (5FU) phacotrabeculectomies compared with 5-fluorouracil trabeculectomies. MethodsA retrospective, nonrandomized study of consecutive primary 5FU phacotrabeculectomies and primary 5FU trabeculectomies. The main outcome measures were preoperative and postoperative IOP, number of medications, visual acuity, and complications. ResultsForty-five 5FU phacotrabeculectomies and 47 5FU trabeculectomies were performed with a mean follow-up of 43.1 and 36.6 months, respectively. The absolute success rate as defined as an IOP equal to or less than 16 mm Hg on no glaucoma drops was 62.2% for the phacotrabeculectomy group and 63.8% for the trabeculectomy group. These success rates were not statistically significantly different (log-rank test P=0.81 for absolute success and P=0.29 for relative success). The magnitude of the treatment effect was found to be significantly greater in the T group compared with the PT group (a 44.6% reduction in IOP in the T group compared with a 31.2% reduction in the PT group). The phacotrabectomy group underwent significantly more postoperative 5FU injections compared with the trabeculectomy group (P=0.008). Conclusions5FU phacotrabeculectomy seems to be a safe and effective treatment option in terms of IOP control. Patients with both coexistent glaucoma and cataract could be considered for combined surgery.

Wound healing modulation after glaucoma surgery.

Recent developments in molecular and cell biology have made a major impact on our understanding of the wound healing process and its modification. In this article, the spectrum of therapies that are either currently available or have potential application as modulators of the scarring response following glaucoma surgery are reviewed. Refinement of existing antimetabolite regimens can improve surgical results, especially in carefully selected patient groups. However, the most promising new approach appears to be using molecular-based therapies, such as fully human neutralizing monoclonal antibodies, designed to target specific molecules in the scarring response. Such strategies ultimately offer the potential of safer, more specific, focal, and titratable treatment, with far-reaching clinical applications.

The impact of glaucoma referral refinement criteria on referral to, and first-visit discharge rates from, the hospital eye service: the Health Innovation & Education Cluster (HIEC) Glaucoma Pathways project

To assess the impact of referral refinement criteria on the number of patients referred to, and first‐visit discharges from, the Hospital Eye Service (HES) in relation to the National Institute for Health & Clinical Excellence (NICE) Glaucoma Guidelines, Joint College Group Guidance (JCG) and the NICE commissioning guidance.

A review of the medical treatment of pediatric glaucomas at Moorfields Eye Hospital.

Purpose:To report on the medical treatments used for pediatric glaucomas. Patients and Methods:A retrospective case series consisting of reviewing the medical notes of pediatric glaucoma patients under the care of the Glaucoma Service at Moorfields Eye Hospital NHS Foundation Trust. The medical notes of 200 patients were selected. The following outcomes were assessed: (1) the use of individual medical therapies; (2) the intraocular pressure (IOP) reduction effect of individual medicines; (3) the reporting of side effects. Results:Medicines were prescribed 1592 times (200 patients). The median % IOP reduction for latanoprost 50 mcg/mL was −17.2% and for the topical beta blockers was −17.7% (as monotherapy), with no statistical difference in IOP-lowering effect between all the medicines (P=0.19). Side effects were reported in 19.5% of all patients—the highest occurrence with brimonidine tartrate 0.2% (in 17% patients) and the lowest occurrence with the prostaglandin analogue and prostamide medicines (in 3.8% patients). The combination of dorzolamide hydrochloride 2%, timolol maleate 0.5% had the greatest persistence of 1 year. Conclusions:The IOP-lowering effects of all the glaucoma medicines were not significantly different although the combination of dorzolamide hydrochloride 2%, timolol maleate 0.5% had the greatest persistence.

The effect of changes in referral behaviour following NICE guideline publication on agreement of examination findings between professionals in an established glaucoma referral refinement pathway: The Health Innovation & Education Cluster (HIEC) Glaucoma Pathways project

Aim To investigate whether the publication of the National Institute for Health and Clinical Excellence (NICE) glaucoma guidelines had an effect on the agreement of examination findings between professionals involved in an established glaucoma referral refinement pathway. Methods To report inter-professional agreement for the clinical examination findings of optometrists with a special interest in glaucoma (OSI), optometrists with no specialist interest in glaucoma (non-OSI) and a glaucoma consultant. Part 1 investigated agreement between an OSI and consultant and part 2 investigated agreement of clinical findings between the non-OSI and a specialist clinician (OSI or consultant). Results Part 1: Agreement between OSI and consultant in determining an abnormal intraocular pressure (IOP) (>21 mm Hg) expressed as a percentage positive predictive value (PPPV) was no different pre-NICE (60.6%) and post-NICE (61.4%, p=0.51) guidelines. PPPV for identification of an abnormal optic disc was better pre-NICE (60.6%) than post-NICE (42.7%, p=0.02). The appropriate referral rate for patients referred by an OSI was higher pre-NICE (69.6%) than post-NICE (61.2%) (p=0.07). Part 2: The PPPV between non-OSI and specialist clinician for an abnormal IOP was better pre-NICE (62.5%) than post-NICE (50.9%, p=0.12). This was also observed for abnormal optic discs, 70.0% pre-NICE and 52.9% post-NICE (p=0.04). Conclusions The accuracy for detecting an abnormal IOP by the OSI has remained unchanged post-NICE, but there was a reduction in accuracy in detecting an abnormal optic disc as well as the appropriate referral rate. For the non-OSI, there was a decline in both IOP and optic disc assessment accuracy.