The Finnish current care guideline for open-angle glaucoma.

This article is an English translation of the 4th Finnish Current Care Guideline for diagnostics, treatment and follow-up of primary open-angle glaucoma, normal-tension glaucoma and pseudoexfoliative glaucoma. This guideline is based on systematic literature reviews and expert opinions with Finland's geographical and operational healthcare environment in mind.

Pseudoexfoliation Glaucoma: Clinical Presentation and Therapeutic Options.

Pseudoexfoliation syndrome (PES) is one of the most common causes of open-angle glaucoma, with a higher risk of vision loss, a higher maximum and mean intraocular pressure (IOP) at diagnosis, and a wider range of IOP fluctuation compared to primary open-angle glaucoma. Patients with this syndrome have a ten-fold higher risk of developing glaucoma than the normal population. A definite diagnosis can be made by the observation of pseudoexfoliation material (PEM) on the anterior lens surface, ciliary processes, zonules, and iris. PEM deposits on the zonules may explain the clinically observed zonular weakness and lens subluxation or dislocation. An increased incidence of cataract development is also associated with PES. There is growing evidence for systemic associations of PES with peripheral, cardiovascular, and cerebrovascular system diseases, Alzheimer's disease, hearing loss, and increased plasma homocysteine levels. Indications for surgery are markedly more common in patients with pseudoexfoliation glaucoma than primary open-angle glaucoma. The goal of this article is to review the latest perspectives on the clinical features, therapy, and systemic associations of this clinically and biologically challenging disease.

Pseudoexfoliation syndrome: The critical role of the extracellular matrix in pathogenesis and treatment.

Pseudoexfoliation syndrome (PEXS) is an age-related condition manifesting mainly in ocular tissues. PEXS is manifested through excess aggregation of fibrillary extracellular material at the anterior part of the eye that consists of a plethora of biomolecules, such as different proteoglycans (PGs) and glycosaminoglycans. PEXS is often linked to increased intraocular pressure, and can also lead to pseudoexfoliation glaucoma with very poor prognosis. Various stimuli are known to affect PEXS, including oxidation stress (OS), UV radiation and osmotic pressure. OS, is prominently involved on the progression of the syndrome as it promotes fibrogenesis, possibly via the induction of transforming growth factor-ß (TGF-ß) and other biomolecular effectors. In addition, PEXS initiation is tightly connected with the dysregulation of extracellular matrix (ECM) homeostasis since aberrant expression of ECM molecules is linked to both the accumulation and low degradation of pseudoexfoliation material. This article aims at uncovering the crucial role of various ECM effectors such as lysyl oxidase-like proteins, matrix metalloproteinases, and TGF-ß1, as well as the biochemical pathways involved in the development and the progression of the PEXS.

Evaluation and treatment of glaucoma 24hours a day. Where are we and where are we going? / Evaluación y tratamiento del glaucoma durante las 24 horas del día. ¿Dónde estamos y hacia dónde vamos?

Current management of glaucoma generally involves medical, laser, or surgical treatment in order to achieve an intraocular pressure (IOP) control which is commensurate with either stability or delayed progression of the disease. Although the follow-up of glaucoma patients is usually carried out with sporadic and isolated intraocular pressure measurements, the literature already indicates that this might not the best option to manage glaucoma patients. This article reviews the importance of 24hours intraocular pressure monitoring based on studies and publications that exist in this regard to date. A critical review on the methodology of these publications has been conducted. The need is stressed for further studies on the intraocular pressure patterns in different types of glaucoma, as well as the pattern with different therapies used in glaucoma aimed at optimising the management of the disease.

[Pseudoexfoliation syndrome and pseudoexfoliation glaucoma]. / Syndrome pseudo-exfoliatif et glaucome exfoliatif.

Pseudoexfoliation syndrome is an age-related systemic disease that mainly affects the anterior structures of the eye. Despite a worldwide distribution, reported incidence and prevalence of this syndrome vary widely between ethnicities and geographical areas. The exfoliative material is composed mainly of abnormal cross-linked fibrils that accumulate progressively in some organs such as the heart, blood vessels, lungs or meninges, and particularly in the anterior structures of the eye. The exact pathophysiological process still remains unclear but the association of genetic and environmental factors are thought to play a role in the development and progressive extracellular accumulation of exfoliative material. Hence, LOXL1 gene polymorphisms, responsible for metabolism of some components of elastic fibers and extracellular matrix, and increased natural exposure to ambient ultraviolet or caffeine consumption have been associated with pseudoexfoliation syndrome. Ophthalmological manifestations are commonly bilateral with an asymmetric presentation and can lead to severe visual impairment and blindness more frequently than in the general population, mainly related to glaucoma and cataract. Pseudoexfoliation glaucoma is a major complication of pseudoexfoliation syndrome and represents the main cause of identifiable glaucoma worldwide. Visual field progression is more rapid than that observed in primary open angle glaucoma, and filtering surgery is more frequently required. Nuclear cataract is more frequent and occurs earlier than in the general population. Owing to poorer pupil dilation and increased zonular instability, cataract surgery with pseudoexfoliation is associated with a 5- to 10-fold increase in surgical complications compared to cataract surgery without pseudoexfoliation. Some specific treatments targeting production, formation or accumulation of exfoliative material could improve the prognosis of this syndrome.

Frequency of unplanned interventions in patients attending for a presumed routine glaucoma follow-up appointment.

OBJECTIVE: To determine the frequency of patient visits in which an unplanned treatment modification was required in chronic patients attending a glaucoma clinic for routine follow-up and to identify the treatment interventions most commonly employed. DESIGN: Prospective, cross-sectional study. PARTICIPANTS: A total of 630 previously stable patients attending a glaucoma clinic for routine follow-up. METHODS: This was a single-centre survey of all eligible patients returning to an academic glaucoma clinic. Data regarding whether patients' visit remained routine or required intervention, which clinical parameter had changed, and any alterations in treatment regimens were studied. RESULTS: The percentage of patients found to require a change in management was 20.79% (131 of 630 patients); 16.9% were found to have a cause for change because of glaucoma, and the remaining 4% required intervention because of a nonglaucomatous condition. The most common parameter that changed treatment was intraocular pressure (43.87%), followed by visual fields (21.29%). The frequency of abnormal parameters varied within each subtype of glaucoma. The frequency of treatment changes among those with primary open-angle glaucoma was 22.58% compared with 16.5% of glaucoma suspects, 14% of ocular hypertensives, 32% of pseudoexfoliative glaucoma, and 50% of normal tension glaucoma patients. The most common intervention (32.84%) was a change in antiglaucoma medications. The next most frequent interventions were laser procedures (21.90%) and surgery (16.06%). CONCLUSIONS: This study suggests that a significant minority of patients attending a glaucoma clinic for a routine appointment require treatment modification.

Short-term Results of Trabeculectomy Using Adjunctive Intracameral Bevacizumab: A Randomized Controlled Trial.

PURPOSE: To investigate the outcome of trabeculectomy with or without adjunctive intracameral bevacizumab. MATERIALS AND METHODS: In this prospective, double-blind, randomized clinical trial, 71 patients with primary open-angle or pseudoexfoliation glaucoma were randomly assigned to receive either 1.25 mg intracameral bevacizumab (n=36) or balanced salt solution as placebo (n=35) at the end of trabeculectomy. Success was defined as at least a 30% drop in intraocular pressure (IOP) compared with baseline values and an IOP between 6 and 21 mm Hg at the last postoperative visit with (qualified) or without (complete) glaucoma medications. RESULTS: Thirty-two patients in bevacizumab group and 33 in placebo group completed a mean follow-up of 10.7±2.1 and 10.5±2.5 months, respectively (P=0.731). The mean preoperative IOP was 28.25±5.64 and 29.11±4.65 mm Hg in the bevacizumab and placebo groups, respectively (P=0.485). Last visit IOP was 14.5±3.7 mm Hg in the bevacizumab group and 18.55±3.64 mm Hg in the placebo group (P<0.001). At last visit, complete success was achieved in 26 cases (81.3%) of bevacizumab group and 16 cases (48.5%) of placebo group (P<0.006). Filtering bleb leak during the first postoperative month was seen in 11 (34%) and in 3 (9%) cases of bevacizumab and placebo groups, respectively (P=0.013). CONCLUSIONS: A single 1.25 mg dose of intracameral bevacizumab significantly improves the success of trabeculectomy; however, it increases the risk of early filtering bleb leakage.

Exfoliative glaucoma: new evidence in the pathogenesis and treatment.

Exfoliation or pseudoexfoliation syndrome (PXF) is an age-related ocular and systemic disease in which abnormal extracellular material is produced and accumulates in many tissues. PXF is the most common identifiable cause of open-angle glaucoma (OAG). PXFG is a particularly aggressive type of OAG, which runs with a faster rate of progression and poorer response to medical therapy than primary OAG (POAG). The prevalence of the condition shows huge variations among different population, Scandinavian and Mediterranean race being the most affected. Many genetics and environmental factors are involved in the pathogenesis and remarkable progresses in understanding the involved factors have been achieved in the past years. Population-based studies have identified mutations on the lysil-oxidase-like 1(LOXL1) gene as a risk factor for PXFS. Environmental and behavioral factors such as latitude of residence, caffeine intake, and vitamins deficiency are under investigation for a possible involvement in determining the disease in genetically predisposed individuals. Treatment options are similar to those recommended for POAG. Exfoliation syndrome predisposes to capsular rupture, zonular dehiscence, and vitreous loss during cataract extraction. Laser trabeculoplasty has been demonstrated to show good clinical outcomes in PXF patients. A review of the current literature and scientific evidences on pathogenesis and treatment is presented.

Prevalence and Prognosis of Pseudoexfoliation Glaucoma in Western India.

PURPOSE: To investigate the prevalence and reconnoiter treatment modalities for Pseudoexfoliation Glaucoma (PXG) in subjects with Pseudoexfoliation Syndrome (PXF) in a rural scenario of western India. DESIGN: A prospective prevalence study. METHODS: Occurrence of PXG in 250 subjects with PXF was studied in the Department of Glaucoma, Shri Ganapati Netralaya, Jalna, India, from 2009 to 2011. The subject pool presented with PXF, having intraocular pressure (IOP) ≥ 20 mm of Hg, and evidencing optic nerve damage and abnormal visual fields were judiciously selected as PXG cohorts. A decision table is formulated to assist the physician in rendering medical or surgical treatment options. RESULTS: The prevalence of PXG increased with increasing age at 30% (95% CI: 28.56-33.72) in the 60-year-old and older population. It was predominantly higher in cohorts involved in outdoor physical activities at 46% (95% CI: 41.24-52.38). The eminence and prevalence of nuclear cataract in subjects with PXG was 72 % (95% CI: 65.72-76.34). Visual impairment was highly prevalent in 75% (95% CI: 73.43-78.29) and 10% (95% CI: 6.87-13.21) cohorts with PXG and PXF respectively. In general, linear modelling IOP was 26.37±1.64 in subjects with PXG, which was managed to 16.50±1.32 after rendering our adapted treatment protocols. CONCLUSIONS: Increased IOP, occludable angles, and glaucomatous optic neuropathy occur more frequently in the population with PXF. It is inferred that that treatment protocol of combined cataract and glaucoma surgery gives maximum reduction in IOP.

Role of subconjunctival bevacizumab as an adjuvant to primary trabeculectomy: a prospective randomized comparative 1-year follow-up study.

PURPOSE: To compare the safety and efficacy of primary trabeculectomy with adjunctive subconjunctival bevacizumab with that of primary trabeculectomy with mitomycin C (MMC). MATERIALS AND METHODS: Forty-two patients with primary open-angle glaucoma were studied. Randomly, subject's eyes underwent primary trabeculectomy with either subconjunctival bevacizumab (2.5 mg/0.1 mL) or topical MMC (0.2 mg/mL for 3 min). The intraocular pressure (IOP) was the primary outcome measure. Secondary outcome measures included the corrected distance visual acuity, number of antiglaucoma medications, postoperative interventions and complications, bleb evaluation (on the basis of Moorfields Bleb Grading System), and the percentage of eyes achieving target pressure of 21, 18, 15, and 12 mm Hg at 6 and 12 months postoperatively. RESULTS: Of the 42 eyes, 21 treated with subconjunctival bevacizumab while 21 were treated with MMC. The mean preoperative IOP in the bevacizumab group improved from 23.9 ± 2.7 mm Hg with 2.6 ± 0.7 antiglaucoma medications to 13.9 ± 2.8 mm Hg with 0.6 ± 0.9 antiglaucoma medications at 12 months (P<0.001 and P<0.001, respectively). The mean preoperative IOP in MMC group improved from 22.9 ± 2.6 mm Hg with 2.7 ± 0.8 antiglaucoma medications to 12.2 ± 3.2 mm Hg with 0.1 ± 0.5 antiglaucoma medications at 12 months (P<0.001 and P<0.001, respectively). At 12 months, 15 of 21 (71%) eyes in the MMC group met a target IOP of 12 mm Hg without antiglaucoma medication while 7 of 21 (33%) eyes in the bevacizumab group did (P=0.02). Encapsulated bleb was seen in 2 (10%) patients in MMC group and in 6 (29%) patients in bevacizumab group (P=0.23). CONCLUSIONS: Although subconjunctival bevacizumab is effective and safe in primary trabeculectomy, IOP control appears to be superior with MMC, in terms of complete success with a target IOP<12 mm Hg and number of antiglaucoma medications required postoperatively.

Washout of pseudoexfoliation material combined with cataract surgery: a new surgical approach to lower intraocular pressure in pseudoexfoliation syndrome.

Glaucoma or ocular hypertension can be caused by the presence of pseudoexfoliation (PEX) material and/or pigmented cells in the trabecular meshwork (TM) and/or in the irido-corneal angle (ICA). Accumulation of this material can be highlighted by slit-lamp (SL), gonioscopy, and ultrasound biomicroscopy (UBM). Such material prevents aqueous humor from flowing out and thus induces intraocular pressure (IOP) elevation. A new technique using a special cannula for washing the TM and ICA, combined with cataract surgery, can lower IOP and reduce the number of hypotensive drugs needed. This study analyzed 11 patients (13 eyes) presenting a pseudoexfoliation glaucoma with cataract. They all had cataract surgery combined with the special washing technique. Visual acuity and IOP were noted before surgery, just after surgery and during follow-up. The number of hypotensive drugs needed was also recorded. Mean follow-up time was 34.4 months (range 21.8-59.2). The first case underwent surgery in 2007 and has a 5-year follow-up time. Local status was controlled by SL, gonioscopy, and UBM. Mean age was 79 years (range 71.6-86.0). Mean visual acuity was 0.37 pre-op (range 0.05-0.6) and 0.89 post-op (range 0.05-1.0). Mean IOP before and after surgery was 32.8 ± 8.7 mmHg (range 20-53) and 15.1 ± 3.5 mmHg (range 10-20), respectively. The amount of hypotensive drugs needed was 87 % lower after surgery. No PEX material recurrence was seen with SL, gonioscopy, and UBM during the mean follow-up of 3 years. No complication was recorded in this study. Cataract surgery combined with the new washout technique of the TM and ICA to remove PEX material or pigmented cells significantly lowers IOP and the amount of drugs needed. Long-term follow-up gives good results with no complication or recurrence. Eye status after surgery remains physiological and further glaucoma surgery can be performed if necessary. More research with a higher number of patients should be initiated to confirm this technique.

Two-year outcome of repeat trabeculectomy with mitomycin C in primary open-angle and PEX glaucoma.

PURPOSE: To evaluate the effectiveness of repeat trabeculectomy with risk factor-adjusted mitomycin C (MMC) application in primary open-angle glaucoma (POAG) and pseudoexfoliation glaucoma (PEXG) over 2 years. METHODS: A total of 58 patients (43 with POAG, 15 with PEXG) who had undergone repeat trabeculectomy with MMC were included in this retrospective study. Exposure time of MMC 0.3 mg/mL was adjusted according to a standardized protocol. Main outcome measures were best-corrected visual acuity (BCVA), intraocular pressure (IOP) reduction, surgical success rate (criteria were defined as A: IOP ≤21 mm Hg and a reduction of IOP ≥20%; B: IOP ≤18 mm Hg and a reduction of IOP of ≥30%; C: IOP ≤15 mm Hg and a reduction of IOP of ≥40% from baseline), and number of medications at baseline, 3 months, and 2 years postoperatively. RESULTS: The BCVA remained stable for 2 years after surgery (0.47 ± 0.47 at baseline, 0.49 ± 0.64 logMAR units after 2 years, respectively). Mean IOP decreased from 22.2 ± 7.0 mm Hg at baseline to 12.7 ± 3.1 mm Hg at 3 months and 12.9 ± 4.3 mm Hg 2 years after surgery. The qualified success rate for criterion A was 75.4%, for criterion B 66.6%, and for criterion C45.6%. Complete success rates were 42.9%, 37.5%, and 32.1%, respectively. Two years after repeat trabeculectomy, the mean IOP was reduced by 38.8%, and the number of medications was reduced significantly. CONCLUSIONS: Repeat trabeculectomy with MMC is successful at lowering IOP in POAG and PEXG and permits a significant and safe reduction of antiglaucomatous medication for at least 2 years after surgery.

Does the use of preoperative antiglaucoma medications influence trabeculectomy success?

PURPOSE: To investigate the influence of preoperative antiglaucoma medications on trabeculectomy outcome. METHODS: Two hundred fifteen eyes, which underwent primary trabeculectomy, were retrospectively analyzed. The average follow-up was 39.8±30.3 months. The only cases of primary open-angle glaucoma, with or without pseudoexfoliation (PXF), were included. "Complete success" was defined as intraocular pressure (IOP) <18 mmHg without glaucoma medications, whereas relative success was defined as the same IOP target with medications. The influence of the preoperatively used glaucoma medications on surgical success was analyzed by univariate Pearson correlation and multivariate (ordinal) regression analysis. RESULTS: There were 118 male (54.9%) and 97 female (45.1%) patients with a mean age of 66.9±9.3 years. PXF glaucoma (PXFG) was present in 93 eyes (43.3%). In 33 patients (15.3%), diabetes mellitus (DM) was present. Complete success was achieved in 116 eyes (54%), relative success in 81 eyes (37.6%), and failure in 18 eyes (8.4%). Neither the total number nor the duration of glaucoma medications used before trabeculectomy was found to have any statistically significant influence on surgical success. In statistical analysis, a combination of topical beta-blocker and carbonic anhydrase inhibitor (BB+CAI) used before surgery was found to be associated with statistically better outcome, whereas the preoperative use of topical beta-blockers alone could have a negative influence on success. PXF was shown to be independently associated with trabeculectomy outcome on multivariate regression analysis. CONCLUSION: The glaucoma medications used preoperatively were not found to have any statistically significant negative influence on the trabeculectomy outcome and use of the combined BB+CAI preparation could have a positive influence, whereas the use of topical beta-blockers alone could have a negative influence on success, although not statistically significant. The presence of PXF was independently associated with a better surgical outcome.

Pseudoexfoliación y catarata / Pseudoexfoliation and cataract

El síndrome de pseudoexfoliación es un desorden sistémico de la matriz extracelular relacionado con la edad, que no solo causa glaucoma crónico de ángulo abierto y catarata, sino que también se relaciona con complicaciones intraoculares espontáneas y quirúrgicas. Las investigaciones recientes han permitido entender sus efectos en tejidos oculares al mejorar los criterios diagnósticos, aplicar nuevos tratamientos y desarrollar nuevas estrategias preventivas para disminuir las complicaciones quirúrgicas. Los nuevos conceptos de patología genética describen al síndrome de pseudoexfoliación como una microfibrilopatía que involucra al factor de crecimiento B-1, el estrés oxidativo y el daño a los mecanismos de protección celular. Se hace una valoración clínica y quirúrgica del glaucoma y la catarata en presencia de pseudoexfoliación.

Pseudoexfoliation syndrome is an age-related generalized fibrotic matrix disorder, which may not only cause chronic open angle glaucoma and cataract, but also a range of other serious spontaneous and surgical intraocular complications. Recent research studies have led to better understanding of effects of the pseudo exfoliation process on ocular tissues by refining diagnostic criteria, applying new therapeutic regimes, and by developing new preventive strategies to reduce surgical complications. The new pathogenetic concepts describe pseudoexfoliation syndrome as microfibrillopathy involving transforming growth factor-B1, oxidative stress, and impaired cellular protection mechanisms. A clinical and surgical evaluation of glaucoma and cataract in patients with pseudoexfoliation was presented in this article.

Managing advanced unilateral pseudoexfoliative glaucoma.

The only proven therapy for glaucoma is intraocular pressure (IOP) reduction, which can be accomplished by different means. Each should be properly discussed with patients in order to best preserve visual function and quality of life. We report a case of unilateral pseudoexfoliative glaucoma, treated for years with triple topical IOP-lowering drugs. The patient presented with advanced optic neuropathy and important ocular side effects secondary to the treatment. Having discussed his options and prognosis, laser trabeculoplasty was performed while maintaining the remaining therapy considering the advanced stage of glaucoma. His IOP was effectively reduced and no progression was noted after 1-year follow-up. Although medical therapy is the mainstream in glaucoma management, its side effects should not be ignored, especially in unilateral cases. Surgery might have been a better solution, but we chose to perform laser trabeculoplasty, an effective and safer alternative, considering the unlikely but serious risk of the "wipe-out phenomenon" in this case.

[Pseudoexfoliative glaucoma]. / Glaucomul pseudoexfoliativ.

DEFINITION: Secondary open-angle glaucoma, characterized by the deposition of whitish, fibrillar material within the structures of the anterior segment of the eye.

Pigment dispersion glaucoma induced by the chafing effect of intraocular lens haptics in Asian eyes.

PURPOSE: To study the possible mechanism and treatment for pigment dispersion glaucoma (PDG) caused by single-piece acrylic (SPA) intraocular lens (IOL) ciliary sulcus fixation in Asian eyes. MATERIALS AND METHODS: Patients referred for PDG caused by SPA IOL ciliary sulcus fixation to our hospital from April 2005 to June 2011 were included. The patients' general information, IOL type, interval between initial surgery and PDG occurrence, examination findings, antiglaucoma medicine regimen and surgical interventions were recorded. RESULTS: In total, six eyes from five Chinese patients were included in this study. The intraocular pressure (IOP) increased 19-30 days after cataract surgery and was not satisfactorily controlled with antiglaucoma medication. Dense pigmentation was deposited on the IOLs and on the anterior chamber angle. IOL haptic chafing was noted on the rear iris surface. IOL repositioning in the capsular bag was performed in three eyes and was combined with trabeculectomy in two eyes with progressive glaucoma. An IOL exchange with three-piece IOL ciliary sulcus fixation was performed in the other three eyes. Scanning electron microscopy of the explanted IOLs demonstrated a rough edge on the IOL haptics. CONCLUSIONS: SPA IOLs were not suitable for ciliary sulcus fixation. The chafing effect of the IOL haptics on the posterior iris pigment epithelium could induce PDG in Asian eyes. IOLs should be positioned in the capsular bag or a three-piece IOL should be used instead.

Cases of pseudophakic pseudoexfoliation in glaucoma patients.

We present cases of primary open angle glaucoma patients without previous history of pseudoexfoliation who developed pseudoexfoliative materials on the anterior surface of the intraocular lens after cataract surgery. Among 5 unilateral pseudophakic pseudoexfoliation cases, 3 showed a more advanced state of glaucoma in the affected eye. The other 2 cases showed progression of glaucoma in the affected eye after the development of pseudophakic pseudoexfoliation, while the unaffected eyes remained stable. In the latter 2 cases, control of intraocular pressure was difficult, and more glaucoma medication was needed in the affected eye. Pseudophakic pseudoexfoliation in glaucoma patients with no history of pseudoexfoliation syndrome or pseudoexfoliative glaucoma has not been reported. In our cases, the eyes which developed pseudophakic pseudoexfoliation showed a more advanced state of glaucoma, more difficulty controlling intraocular pressure, and faster progression of glaucoma. More observation is needed, but we cautiously postulate that pseudophakic pseudoexfoliation may have a role as a clinical risk factor in the prediction of glaucoma progression.