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Purpose

To report a new familial case of the recently described autosomal recessive syndrome of nanophthalmos-retinitis pigmentosa-foveoschisis-optic disc drusen, which arises from compound heterozygosity for Membrane Frizzled-Related Protein (MFRP) mutations in a sibling pair of Mexican origin.

Methods

Ophthalmological assessment included slit-lamp and dilated fundus examination, applanation tonometry, fundus photography, A-mode and B-mode ultrasound examination, electroretinogram, fluorescein retinal angiography, optical coherence tomography, and electrooculogram in both affected siblings. Molecular genetic analysis consisted of PCR amplification and direct automated sequence of the complete coding region of the MFRP gene. In addition, allele-specific cloning and sequencing techniques were used to characterize a heterozygous MFRP frameshift mutation.

Results

Clinical examination revealed high hyperopia of > +16 diopters while electroretinographic and fluorangiographic studies demonstrated a retinal dystrophy compatible with retinitis pigmentosa. Ultrasound examination showed nanophthalmos (eye axial length <15 mm) and optic disc drusen while optical coherence tomography evidenced cystoid macular edema. Nucleotide sequencing in DNA from both affected siblings disclosed the presence of two MFRP mutations: a novel heterozygous point mutation predicting a nonsense change from tyrosine (TAC) to a stop signal (TAA) at codon 317, and a heterozygous 1 bp deletion in exon 5, predicting a prematurely truncated protein (p.Asn167ThrfsX25).

Discussion

The third known family with the syndrome of nanophthalmos-retinitis pigmentosa-foveoschisis-optic disc drusen is presented. This is the first demonstration of compound heterozygosity for MFRP mutations as the source of the disease. The affected siblings described here are the youngest patients with the disease reported to date and the comparison of their clinical data with previous individuals with this syndrome suggest that some aspects of the phenotype are probably age-dependent.

An unusual case of bilateral nanophthalmos with pigmentary retinal dystrophy and angle closure glaucoma is presented. This is probably the first published report of the established association of all these three entities in the same patient. The aetiological possibilities and clinical significance are discussed.

Images

Aim: Using the newly developed scanning peripheral anterior chamber depth analyser (SPAC), the effects of peripheral laser iridotomy (PLI) on peripheral anterior chamber depth (PACD) were determined quantitatively as was the association between PACD and chronic elevation of intraocular pressure (IOP) after PLI.

Methods: 16 eyes of 15 patients with acute primary angle closure glaucoma (PACG) attack, 14 eyes of 14 patients with narrow angle and PACG attack in their fellow eyes, and 13 eyes of seven patients with chronic angle closure glaucoma (CACG) were enrolled. The SPAC scanned the anterior ocular segment from the optical axis to the limbus and took 21 consecutive slit lamp images at 0.4 mm intervals. A computer installed program automatically evaluated the PACD and the averaged values of three measurements were employed for analysis.

Results: PLI significantly increased PACD and changed the iris contour from convex to flat or concave in all the enrolled eyes. The extent of the PLI induced PACD increase was enhanced with increasing distance from the optical axis. Comparing PACDs after PLI, eyes that received prophylactic PLI showed the greatest extent of PLI induced PACD increase, followed by eyes with CACG and eyes with PACG attack. The PACD of eyes with PACG attack was almost the same as that of the fellow eyes of PACG attack before prophylactic PLI. Eyes with PACG attack showed poorer IOP control after PLI than eyes with narrow angle and CACG with PLI.

Conclusions: PLI significantly increases PACD and the small PLI induced opening of PACD may contribute to chronic IOP elevation after PLI.

Changes in ocular findings have been noted in association with several metabolic diseases.

In homocystinuria the crystalline lens in the majority of cases is subluxated inferiorly, while in Marfan's syndrome the dislocation was upward.

In cystinosis, slit-lamp examination reveals numerous gold crystal-like cystine deposits in both the cornea and bulbar conjunctiva.

Patients with galactosemia have cataracts of the “oil drop” type, which usually can be seen with an ophthalmoscope even though the opacity is not dense.

Eight patients with Lowe's syndrome who were observed had cataracts, and four of them had severe glaucoma.

Three of five patients with glycogen storage disease Type I had yellowish deposits in the macular and paramacular areas, thought to be due to hypercholesterolemia.

Images

AIMS—To evaluate central corneal thickness determined by optical coherence tomography (OCT) in various types of glaucoma, and its influence on intraocular pressure (IOP) measurement.
METHODS—Central corneal thickness (CCT) was determined by using OCT in 167 subjects (167 eyes). 20 had primary open angle glaucoma (POAG), 42 had low tension glaucoma (LTG), 22 had ocular hypertension (OHT), 10 had primary angle closure glaucoma (AC), 24 had pseudoexfoliation glaucoma (PEX), 13 had pigmentary glaucoma (PIG), and 36 were normal.
RESULTS—CCT was significantly higher in ocular hypertensive subjects (593 (SD 35) µm, p <0.0001) than in the controls (530 (32) µm), whereas patients with LTG (482 (28) µm, p < 0.0001), PEX (493 (33) µm, p <0.0001), and POAG (512 (30) µm, p <0.05) showed significantly lower readings. There was no statistically significant difference between the controls and patients with PIG (510 (39) µm) and AC (539 (37) µm).
CONCLUSIONS—Because of thinner CCT in patients with LTG, PEX, and POAG this may result in underestimation of IOP, whereas thicker corneas may lead to an overestimation of IOP in subjects with OH. By determining CCT with OCT, a new and precise technique to measure CCT, this study emphasises the need for a combined measurement of IOP and CCT in order to obtain exact IOP readings.



Purpose

The membrane frizzled-related protein (MFRP) has been proposed as a probable candidate gene for extreme hyperopia and nanophthalmos, which are factors for angle-closure glaucoma. The purpose of our study was to investigate whether there are significant associations between angle-closure glaucoma and sequence variants in the MFRP gene reported previously in Taiwanese subjects.

Methods

Genomic DNA was collected from 63 subjects with angle-closure glaucoma and 66 age-matched and gender-matched controls without angle-closure glaucoma. Three sequence variants were detected by polymerase chain reaction (PCR) and direct sequencing in all of the cases and controls.

Results

None of the three sequence variants showed a significant result in terms of association with disease. The pairwise linkage disequilibrium (LD) mapping confirmed that these alleles have a comparatively strong LD index greater than 0.7 for D' and greater than 0.4 for r2 at these polymorphisms. However, we found there were no statistical associations between any of the three sequence variants located on MFRP and angle-closure glaucoma.

Conclusions

In our pilot study, variations that we tested in MFRP were not associated with the development of acute angle-closure glaucoma in Taiwanese subjects.

Purpose:

To evaluate the intraocular pressure (IOP)-lowering efficacy of goniosynechialysis (GSL) for advanced chronic angle-closure glaucoma (CACG) using a simplified slit-lamp technique.

Patients and methods:

Patients with CACG with one severely affected eye with best-corrected visual acuity below 20/200 and a mildly or functionally unaffected fellow eye were enrolled in this study. All patients underwent ophthalmologic examinations including measurement of visual acuity, best-corrected visual acuity, and IOP; biomicroscopy; specular microscopy; fundus examination; and gonioscopy followed by anterior chamber paracentesis and GSL for nasal peripheral anterior synechiae in the eye with severe CACG.

Results:

Thirty patients (18 men, 12 women) were identified as having CACG with an initial mean IOP of 47.1 ± 6.7 mmHg (range 39–61 mmHg) in the severely affected eye. One week after GSL, the mean IOP of the treated eyes decreased to 19.3 ± 2.8 mmHg (range 14–26 mmHg) without antiglaucoma medication (average decrease 27.7 ± 6.5 mmHg; range 16–41 mmHg), which was significant (P < 0.00001) compared with baseline. After an average follow-up period of 36.6 ± 1.0 months (range 35–38 months), the mean IOP stabilized at 17.4 ± 2.2 mmHg (range 12–21 mmHg). The nasal angle recess did not close again in any one of the patients during the follow-up period. The average significant (P < 0.00001) decrease in corneal endothelial cell density in the treated eyes was 260 ± 183 cells/mm2 (range 191–328 cells/mm2).

Conclusions:

Anterior chamber paracentesis and GSL lowers IOP in advanced CACG, though it may lead to mild corneal endothelial cell loss.

Video abstract

Video

Purpose

The genetic basis of primary angle closure glaucoma (PACG) has yet to be elucidated. Ocular characteristics related to PACG such as short hyperopic eyes with shallow anterior chambers suggest the involvement of genes that regulate ocular size. CHX10, a retinal homeobox gene associated with microphthalmia, and MFRP, the membrane-type frizzled-related protein gene underlying recessive nanophthalmos, represent good candidate genes for PACG due to the association with small eyes. To investigate the possible involvement of CHX10 and MFRP in PACG, we sequenced both genes in PACG patients with small ocular dimensions.

Methods

One hundred and eight Chinese patients with axial lengths measuring 22.50 mm or less were selected for analysis. Ninety-three age- and ethnically-matched control subjects were also screened. Genomic DNA was extracted from leukocytes of peripheral blood samples, and the exons of CHX10 and MFRP were amplified by polymerase chain reaction (PCR) and subjected to bidirectional sequencing and analysis.

Results

All study patients were Chinese with a mean age of 66.2±9.1 years (range 46–86). There were 77 females (71.3%). Forty-nine out of the one hundred and eight subjects had previous symptomatic PACG, and 59 had asymptomatic PACG. The mean axial length was 21.90±0.50 mm (range 19.98–22.50 mm). We identified a possible disease-causing variant in CHX10 (c.728G>A) resulting in Gly243Asp substitution in one patient. This variant was not found in 215 normal controls. Several CHX10 and MFRP polymorphisms were also identified.

Conclusions

Our results do not support a significant role for CHX10 or MFRP mutations in PACG.

Purpose

To assess the safety and efficacy of transitioning patients whose intraocular pressure (IOP) had been insufficiently controlled on prostaglandin analog (PGA) monotherapy to treatment with travoprost 0.004%/timolol 0.5% fixed combination with benzalkonium chloride (TTFC).

Methods

This prospective, multicenter, open-label, historical controlled, single-arm study transitioned patients who had primary open-angle glaucoma, pigment dispersion glaucoma, or ocular hypertension and who required further IOP reduction from PGA monotherapy to once-daily treatment with TTFC for 12 weeks. IOP and safety (adverse events, corrected distance visual acuity, and slit-lamp biomicroscopy) were assessed at baseline, week 4, and week 12. A solicited ocular symptom survey was administered at baseline and at week 12. Patients and investigators reported their medication preference at week 12.

Results

Of 65 patients enrolled, 43 had received prior travoprost therapy and 22 had received prior nontravoprost therapy (n = 18, bimatoprost; n = 4, latanoprost). In the total population, mean IOP was significantly reduced from baseline (P = 0.000009), showing a 16.8% reduction after 12 weeks of TTFC therapy. In the study subgroups, mean IOP was significantly reduced from baseline to week 12 (P = 0.0001) in the prior travoprost cohort (19.0% reduction) and in the prior nontravoprost cohort (13.1% reduction). Seven mild, ocular, treatment-related adverse events were reported. Of the ten ocular symptom questions, eight had numerically lower percentages with TTFC compared with prior PGA monotherapy and two had numerically higher percentages with TTFC (dry eye symptoms and ocular stinging/burning). At week 12, TTFC was preferred over prior therapy for 84.2% of patients (48 of 57) by the patients themselves, and for 94.7% of patients (54 of 57) by their physicians.

Conclusion

When TTFC replaced PGA monotherapy in patients whose IOP had been uncontrolled, the outcome was a significant reduction in IOP and an acceptable safety and tolerability profile. Most patients and investigators preferred TTFC to prior PGA monotherapy.

Cystinosis is a rare autosomal recessive metabolic disorder characterized by the intracellular accumulation of cystine, the disulfide of the amino acid cysteine, in many organs and tissues. Infantile nephropathic cystinosis is the most severe phenotype. Corneal crystal accumulation and pigmentary retinopathy were originally the most commonly described ophthalmic manifestations, but successful kidney transplantation significantly changed the natural history of the disease. As cystinosis patients now live longer, long-term complications in extrarenal tissues including the eye, have become apparent. A case of an adult patient with infantile nephropathic cystinosis is reported. He presented with many long-term ocular complications of cystinosis. After 4 years of follow-up, the patient died from sepsis. Pathology of the phthisical eyes demonstrated numerous electron transparent polygonal spaces, bounded by single membrane, in corneal cells, retinal pigment epithelial cells, and even choroidal endothelial cells. The ophthalmic manifestations and pathology of infantile nephropathic cystinosis are discussed and reviewed in light of the current report and other cases in the literature.

Aim

To report a preliminary study on the safety and efficacy of the use of a cheese‐wire suture in trabeculectomy.

Patients and methods

The case notes of 32 eyes of 25 patients with medically uncontrolled glaucoma who underwent trabeculectomy with cheese‐wire suture at Stobhill Hospital, Glasgow, UK, between July 2001 and September 2002 were studied retrospectively. Diagnoses included primary open angle glaucoma (n = 24), normal tension glaucoma (n = 3), angle closure glaucoma (n = 2), ocular hypertension (n = 1), angle recession glaucoma (n = 1) and combined mechanism glaucoma (n = 1). The mean presenting intraocular pressure (IOP) was 29.5 mm Hg and mean intraocular pressure before operation was 23.5 mm Hg

Outcome measures

Success was defined as lowering of IOP by at least 15% compared with IOP before removal.

Results

A total of 20 eyes (62%) underwent removal of the cheese‐wire suture. 17 eyes (85%) underwent removal for therapeutic reasons (failing/failed blebs) and three eyes (15%) underwent suture removal as the suture loops were exposed. The timing of removal was between 2 weeks and 12 months following surgery. A successful outcome was seen in 12/17 (70%) eyes in the eyes that had therapeutic suture removal. 15 eyes had undergone previous surgical interventions (trabeculectomy n = 12, extracapsular cataract extraction n = 1 and laser peripheral iridotomies n = 2). Mean IOP before removal was 23.66 mm Hg and mean IOP immediately following removal was 11.33 mm Hg. Of the 32 eyes that underwent trabeculectomy with cheese‐wire suture, 24 eyes had intraoperative mitomycin C and one eye had 5‐fluorouracil. The remaining seven eyes did not have any antimetabolites. Early complications related to the surgical procedure included conjunctival haematoma in one eye (3%), corneal abrasion in one eye (3%), wound leak in five eyes (15%), shallow anterior chamber in one eye (3%), hyphaema in six eyes (18%), choroidal effusion in six eyes (18%) and raised IOP in two eyes (6%). Late complications of suture exposure occurred in three eyes (9%). Complications related to removal of the cheese‐wire suture included suture breakage in two eyes (10%), hypotony in one eye (5%) and transient hyphaema in one eye (5%).

Conclusion

The use of cheese‐wire suture in trabeculectomy appears to be safe and may provide an alternative strategy in the management of bleb failure.

Purpose

To report a case of acute angle-closure glaucoma resulting from spontaneous hemorrhagic retinal detachment.

Methods

An 81-year-old woman visited our emergency room for severe ocular pain and vision loss in her left eye. Her intraocular pressures (IOPs) were 14 mmHg in the right eye and 58 mmHg in the left eye. Her visual acuity was 0.4 in the right eye but she had no light perception in the left eye. The left anterior chamber depth was shallow and gonioscopy of the left eye showed a closed angle. In comparison, the right anterior chamber depth was normal and showed a wide, open angle. Computed tomography and ultrasonography demonstrated retinal detachment due to subretinal hemorrhage. After systemic and topical antiglaucoma medications failed to relieve her intractable severe ocular pain, she underwent enucleation.

Results

The ocular pathology specimen showed that a large subretinal hemorrhage caused retinal detachment and pushed displaced the lens-iris diaphragm, resulting in secondary angle-closure glaucoma.

Conclusions

Prolonged anticoagulant therapy may cause hemorrhagic retinal detachment and secondary angle-closure glaucoma. If medical therapy fails to relieve pain or if there is suspicion of an intraocular tumor, enucleation should be considered as a therapeutic option.

PURPOSE: Angle-closure glaucoma is rare in children and young adults. Only scattered cases associated with specific clinical entities have been reported. We evaluated the findings in patients in our database aged 40 or younger with angle closure. METHODS: Our database was searched for patients with angle closure who were 40 years old or younger. Data recorded included age at initial consultation; age at the time of diagnosis; gender; results of slit-lamp examination, gonioscopy, and ultrasound biomicroscopy (from 1993 onward); clinical diagnosis; and therapy. Patients with previous incisional surgery were excluded, as were patients with anterior chamber proliferative mechanisms leading to angle closure. RESULTS: Sixty-seven patients (49 females, 18 males) met entry criteria. Mean age (+/- SD) at the time of consultation was 34.4 +/- 9.4 years (range, 3-68 years). Diagnoses included plateau iris syndrome (35 patients), iridociliary cysts (8 patients), retinopathy of prematurity (7 patients), uveitis (5 patients), isolated nanophthalmos (3 patients), relative pupillary block (2 patients), Weill-Marchesani syndrome (3 patients), and 1 patient each with Marfan syndrome, miotic-induced angle closure, persistent hyperplastic primary vitreous, and idiopathic lens subluxation. CONCLUSION: The etiology of angle closure in young persons is different from that in the older population and is typically associated with structural or developmental ocular anomalies rather than relative pupillary block. Following laser iridotomy, these eyes should be monitored for recurrent angle closure and the need for additional laser or incisional surgical intervention.

Purpose

To investigate the role of MYOC and CYP1B1 in Iranian juvenile open angle glaucoma (JOAG) patients.

Methods

Twenty-three JOAG probands, their available affected and unaffected family members, and 100 ethnically matched control individuals without history of ocular disease were recruited. Clinical examinations of the probands included slit lamp biomicroscopy, intraocular pressure (IOP) measurement, gonioscopic evaluation, fundus examination, and perimetry measurement. Familial cases were classified according to the mode of inheritance. Exons of MYOC and CYP1B1 were sequenced, and novel variations assessed in the control individuals. Potential disease-associated variations were tested for segregation with disease status in available family members.

Results

The mode of inheritance of the disease in the families of four probands (17.4%) appeared to be autosomal dominant and in at least eight (34.8%) to be autosomal recessive. Four patients carried MYOC mutations, and an equal number carried CYP1B1 mutations. The MYOC mutations were heterozygous; two of them (p.C8X and p.L334P) are novel, and one codes for the shortest truncated protein so far reported. Autosomal recessive inheritance was consistent with inheritance observed in families of patients carrying CYP1B1 mutations. All these patients carried homozygous mutations.

Conclusions

MYOC and CYP1B1 contributed equally to the disease status of the Iranian JOAG patients studied. The contribution of the two genes appeared to be independent in that no patient carried mutations in both genes. The fraction of Iranian patients carrying MYOC mutations was comparable to previously reported populations.

Background

The relationship between intraocular pressure (IOP) changes and hemodialysis has been evaluated for several decades. However, no report on an IOP rise in uveitis patients during hemodialysis has been previously documented. This report describes the case of an uveitis patient with repetitive IOP spikes associated with severe ocular pain during hemodialysis sessions, which resolved after glaucoma filtering surgery.

Case presentation

A 47-year-old male with diabetes and hypertension had complained of recurrent ocular pain in the left eye during hemodialysis sessions. A slit-lamp examination showed diffuse corneal epithelial edema with several white keratic precipitates and inflammatory cells (Grade 3+) in the anterior chamber of the left eye. No visible neovascularization or synechiae were visible on the iris or angle. Topical glaucoma eye-drops and intravenous mannitol before hemodialysis did not prevent subsequent painful IOP spikes in the left eye. At the end of hemodialysis, IOP averaged ~40 mmHg. After trabeculectomy with mitomycin C in the left eye, his IOP stabilized in the low-teens (range, 10–14 mmHg) and no painful IOP spikes occurred during hemodialysis over the first postoperative year.

Conclusion

We present a case of recurrent painful IOP spikes during hemodialysis in a patient with unilateral anterior uveitis unresponsive to conventional medical treatment prior to hemodialysis. To our knowledge, this is the first case report of repetitive symptomatic IOP rise during hemodialysis in an uveitic glaucoma patient. This case highlights the importance of the awareness of the possibility that IOP may rise intolerably during hemodialysis in uveitis patients with a compromised outflow facility.

Purpose

To report a case of bilateral acute myopia and angle closure glaucoma after ingestion of methazolamide.

Methods

An interventional case report of a 70-year-old male who developed bilateral, acute myopia and angle closure glaucoma after ingesting methazolamide tablets for the treatment of normal tension glaucoma.

Results

Bilateral anterior chamber shallowing associated with ciliary body edema, supraciliary effusions, and shallow posterior choroidal effusions were documented with slit-lamp photography and high-frequency ultrasonography. Near complete resolution of these signs after discontinuation of methazolamide were also documented.

Conclusion

Methazolamide may be associated with secondary myopia and angle closure glaucoma. Discontinuation of methazolamide leads to resolution of this process, as documented by slit-lamp photography and high-frequency ultrasonography.

The introduction of selective laser trabeculoplasty (SLT) provided a new choice for the reduction of intraocular pressure (IOP) in eyes with open angle glaucoma (OAG) and ocular hypertension (OHT). SLT was demonstrated equally as effective as topical medical therapy and argon laser trabeculoplasty (ALT) to lower IOP. It is a potentially repeatable procedure because of the lack of coagulation damage to the trabecular meshwork (TM) and also effect in patients with previously failed ALT. SLT can be used to treat patients with OAG, pseudoexfoliation glaucoma, pigmentary glaucoma, normal-tension glaucoma, OHT, juvenile glaucoma, pseudophakic and aphakic glaucoma. Furthermore, SLT can be considered as a primary treatment option in patients who cannot tolerate or are noncompliant with medications, while not interfering with the success of future surgery. Its safety profiles include mild and transient inflammation, ocular pain and a small risk of moderate IOP elevations after the procedure. SLT is a safe and effective means of IOP reduction in eyes with OAG and OHT.

Executive Summary

Clinical Need: Condition and Target Population

There are two main types of glaucoma, primary open angle (POAG) and angle closure glaucoma, of which POAG is the more common type. POAG is diagnosed by assessing degenerative changes in the optic disc and loss of visual field (VF). Risk factors for glaucoma include an increase in intraocular pressure (IOP), a family history of glaucoma, older age and being of African descent. The prevalence of POAG ranges from 1.1% to 3.0% in Western populations and from 4.2% to 8.8% in populations of African descent.

Usually the IOP associated with POAG is elevated above the normal distribution (10-20 mmHg), but when IOP is not elevated it is often referred to as normal-tension glaucoma (NTG). In population based studies, approximately one-third to half of the patients with glaucomatous VF loss have normal IOP on initial examination.

People with elevated IOP (>21 mmHg), but with no evidence of optic disc or VF damage have ocular hypertension. It has been estimated that 3 to 6 million people in the United States including 4% to 7% of those older than 40 years have elevated IOP without detectable glaucomatous damage on standard clinical tests. An Italian study found the overall prevalence of ocular hypertension, POAG, and NTG in 4,297 people over 40 years of age to be 2.1%, 1.4% and 0.6% respectively.

Diurnal Curves for Intraocular Pressure Measurement

Diurnal Curve

In normal individuals, IOP fluctuates 2 to 6 mmHg over a 24 hour period. IOP is influenced by body position with higher readings found in the supine relative to the upright position. As most individuals sleep in the supine position and are upright during the day, IOP is higher on average in people, both with and without glaucoma, in the nocturnal period. IOP is generally higher in the morning compared to the afternoon.

Multiple IOP measurements over the course of a day can be used to generate a diurnal curve and may have clinical importance in terms of diagnosis and management of patients with IOP related conditions since a solitary reading in the office may not reveal the peak IOP and fluctuation that a patient experiences. Furthermore, because of diurnal and nocturnal variation in IOP, 24-hour monitoring may reveal higher peaks and wider fluctuations than those found during office-hours and may better determine risk of glaucoma progression than single or office-hour diurnal curve measurements.

There is discrepancy in the literature regarding which parameter of IOP measurement (e.g., mean IOP or fluctuation/range of IOP) is most important as an independent risk factor for progression or development of glaucoma. The potential for increased rates or likelihood of worsening glaucoma among those with larger IOP swings within defined time periods has received increasing attention in the literature.

According to an expert consultant:

The role of a diurnal tension curves is to assess IOP in relationship to either a risk factor for the development or progression of glaucoma or achievement of a target pressure which may direct a therapeutic change.

Candidates for a diurnal curve are usually limited to glaucoma suspects (based on optic disc changes or less commonly visual field changes) to assess the risk for development of glaucoma or in patients with progressive glaucoma despite normal single office IOP measurements.

Clinically diurnal tension curves are used to determine the peak IOP and range.

Single IOP Measurements

Intraocular pressure fluctuation as a risk factor for progression of glaucoma has also been examined without the use of diurnal curves. In these cases, single IOP measurements were made every 3-6 months over several months/years. The standard deviation (SD) of the mean IOP was used as a surrogate for fluctuation since no diurnal tension curves were obtained.

Objective

To determine whether the use of a diurnal tension curve (multiple IOP measurements over a minimum 8 hour duration) is more effective than not using a diurnal tension curve (single IOP measurements) to assess IOP fluctuation as a risk factor for the development or progression of glaucoma.

To determine whether the use of a diurnal tension curve is beneficial for glaucoma suspects or patients with progressive glaucoma despite normal single office IOP measurements and leads to a more effective disease management strategy.

Research Methods

Literature Search

Search Strategy

A literature search was performed on July 22, 2010 using OVID MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations, EMBASE, the Cumulative Index to Nursing & Allied Health Literature (CINAHL), the Cochrane Library, and the International Agency for Health Technology Assessment (INAHTA) for studies published from January 1, 2006 until July 14, 2010. Abstracts were reviewed by a single reviewer and, for those studies meeting the eligibility criteria, full-text articles were obtained. Reference lists were also examined for any additional relevant studies not identified through the search. Articles with unknown eligibility were reviewed with a second clinical epidemiologist, then a group of epidemiologists until consensus was established. The quality of evidence was assessed as high, moderate, low or very low according to GRADE methodology.

Inclusion Criteria

Open angle glaucoma (established or OHT high risk) in an adult population

IOP measurement by Goldmann applanation tonometry (the gold standard)

Number and timing of IOP measurements explicitly reported (e.g., 5 measurements a day for 5 visits to generate a diurnal curve or 1 measurement a day [no diurnal curve] every 3 months for 2 years)

IOP parameters include fluctuation (range [peak minus trough] or standard deviation) and mean

Outcome measure = progression or development of glaucoma

Study reports results for ≥ 20 eyes

Most recent publication if there are multiple publications based on the same study

Exclusion Criteria

Angle closure glaucoma or pediatric glaucoma

Case reports

IOP measured by a technique other than GAT (the gold standard)

Number and timing of IOP measurements not explicitly reported

Outcomes of Interest

Progression or development of glaucoma

Conclusion

There is very low quality evidence (retrospective studies, patients on different treatments) for the use of a diurnal tension curve or single measurements to assess short or long-term IOP fluctuation or mean as a risk factor for the development or progression of glaucoma.

There is very low quality evidence (expert opinion) whether the use of a diurnal tension curve is beneficial for glaucoma suspects or patients with progressive glaucoma, despite normal single office IOP measurements, and leads to a more effective disease management strategy.

Purpose:

To compare the diurnal intraocular pressure (IOP)-lowering efficacy and safety of travoprost 0.004% and tafluprost 0.0015% administered to patients with primary open-angle glaucoma or ocular hypertension.

Methods:

This was a randomized, double-masked, active-controlled, crossover design trial, in which patients were randomized to either travoprost or tafluprost monotherapy administered once daily in the evening for six weeks and then crossed over to the alternative treatment for another six weeks. Diurnal IOP was measured (8 am to 8 pm, every two hours) and a solicited symptom survey was administered at the end of both six-week periods, as was conjunctival hyperemia and visual acuity assessment, slit-lamp biomicroscopy, and adverse event solicitation.

Results:

Fifty-one patients were randomized and 48 patients completed the study. The 12-hour mean diurnal IOP was significantly lower with travoprost therapy than with tafluprost therapy (P = 0.01), and a significantly lower IOP was also reported for travoprost at five of the seven individual time points (P < 0.05). Neither therapy produced a significant increase from baseline in any of the individual patient-reported symptom scores, except for hyperemia (P ≤ 0.01), which was increased with both treatments. Investigator-observed hyperemia was also increased from baseline with both therapies (P < 0.01), although the increase with travoprost therapy was significantly smaller than with tafluprost (P < 0.01). No additional safety concerns were noted from slit-lamp biomicroscopy or visual acuity results, and no difference was noted in patient-reported tolerability of the two medications.

Conclusion:

Travoprost 0.004% monotherapy produced lower diurnal IOP than tafluprost 0.0015% in patients with primary open-angle glaucoma or ocular hypertension and exhibited a similar safety profile.

Patients with nanophthalmos are prone to develop a chronic painless type of glaucoma in middle age, probably due to the natural increase in the size of the lens which is already relatively too large for the small eye. Although the underlying mechanism is obscure, a slowly progressive "creeping" chronic angle-closure is postulated, but gonioscopic evaluation is difficult due to the shallow anterior chamber, with grade I and slit angles. Response to medical treatment is poor and miotics may even make the condition worse by producing relative pupillary block and by relaxing the lens zonule. Ordinary glaucoma surgery is to be avoided in nanophthalmos because of the fear of postoperative ciliary-block malignant glaucoma. Periopheral iridectomy performed in five eyes at an advanced stage of the chronic angle-closure did not facilitate glaucoma control in three eyes, and in two eyes in which the operation was combined with posterior sclerotomy, the eyes became blind from vitreous hemorrhage. Lenx extraction in five eyes controlled the glaucoma but was followed by choroidal effusion and nonrhegmatogenous retinal detachements in two eyes and blindness in another eye when combined with a posterior sclerotomy. No firm therapeutic recommendations can be made on the basis of the author's experience in the six reported cases. Conventional medical therapy seems ineffectual even when begun early in the glaucoma. Conventional glaucoma surgery must be performed early, before permanent damage to the outflow mechanism occurs but removal of the lens must be anticipated. The surgeon must also remain aware of the high incidence of serious posterior-segment complications which inexplicably follow glaucoma or lens surgery in nanophthalmos, as described by Brockhurst.

Images

A pilot study has been carried out to examine the efficacy of diode laser trabeculoplasty in the treatment of primary open-angle glaucoma and ocular hypertension. The device used was portable and could be attached to a standard slit-lamp microscope. Powers of 0.8-1.2 W were used, with a spot size of 100 microns and a pulse of 0.20 second. Laser trabeculoplasty carried out on 20 eyes for glaucoma resulted in a mean ocular hypotensive effect of 10.2 mmHG at two weeks after treatment and of 9.55 mmHg at 6 months. It is concluded that diode laser trabeculoplasty is an effective mode of treatment for eyes with open-angle glaucoma or with ocular hypertension.

Purpose

To assess outcomes following endoscope-assisted pars plana vitrectomy with concurrent pars plana tube shunt placement.

Methods

Records of 18 adult patients (19 eyes) at one institution with uncontrolled chronic angle closure glaucoma (CACG) associated with corneal opacification or fibrosed pupils were retrospectively reviewed. All eyes underwent endoscope-assisted pars plana vitrectomy with Baerveldt tube shunt placement into the vitreous cavity between 1997 and 2005. Intraocular pressure (IOP) reduction, glaucoma medication reduction, complications, and visual acuity were analyzed.

Results

Mean follow-up duration was 62 months (range, 10–106 months). Mean preoperative IOP was 31.3±10.5 (SD) mmHg on 3.4±1.0 (SD) glaucoma medications. IOP was significantly reduced at each postoperative time point examined. In the 17 eyes without phthisis, IOP was significantly reduced at the final follow-up examination to a mean of 11.4±2.9 (SD) mmHg (P<0.0001) on 1.3±1.2 (SD) medications (P<0.0001). No complications occurred in 14 of 19 eyes. Postoperatively, best attained visual acuity improved in 14/19 eyes, remained unchanged in 4/19 eyes, and was reduced in 1/19 eye.

Conclusion

Combined endoscope-assisted pars plana vitrectomy with placement of a Baerveldt tube shunt into the vitreous cavity is a useful intervention in patients with uncontrolled CACG, media opacities, and limited surgical options.

Exfoliation syndrome (XFS) is an age-related, generalized disorder of the extracellular matrix characterized by the production and progressive accumulation of a fibrillar extracellular material in many ocular tissues and is the most common identifiable cause of open-angle glaucoma worldwide. Exfoliation syndrome plays an etiologic role in open-angle glaucoma, angle-closure glaucoma, cataract, and retinal vein occlusion. It is accompanied by an increase in serious complications at the time of cataract extraction, such as zonular dialysis, capsular rupture, and vitreous loss. It is associated systemically with an increasing number of vascular disorders, hearing loss, and Alzheimer's disease. Exfoliation syndrome appears to be a disease of elastic tissue microfibrils. Directed therapy simply means devising specific treatments for specific diseases. There was little incentive to attempt to distinguish between various open-angle glaucomas if the treatments were essentially the same. However, this view also prevented the application of directed therapy in those instances in which such was available and applicable. Pilocarpine has multiple beneficial actions in eyes with XFS. Not only does it lower IOP, but by increasing aqueous outflow, it should enable the trabecular meshwork to clear more rapidly, and by limiting pupillary movement, should slow the progression of the disease. Theoretically, miotics should be the first line of treatment. Pilocarpine 2% q.h.s. can provide sufficient limitation of pupillary mobility without causing these side effects. In 2007, two common single nucleotide polymorphisms in the coding region of the lysyl oxidase-like 1 (LOXL1) gene located on chromosome 15 were specifically associated with XFS and XFG. LOXL1 is a member of the lysyl oxidase family of enzymes, which are essential for the formation, stabilization, maintenance, and remodelling of elastic fibers and prevent age-related loss of elasticity of tissues. LOXL1 protein is a major component of exfoliation deposits and appears to play a role in its accumulation and in concomitant elastotic processes in intra- and extraocular tissues of XFS patients. This discovery should open the way to new approaches and directions of therapy for this protean disorder.

We report on a case of cholesterosis bulbi concurrent with secondary glaucoma. A 36-year-old man, with a history of long-standing retinal detachment in his right eye after the irrigation and aspiration of a congenital cataract, presented with a clinical picture of elevated intraocular pressure and ocular pain. Upon slit-lamp examination, we found a ciliary injection and a pseudohypopyon of polychromatic crystals. Gonioscopic examination revealed a large amount of crystals deposited on the trabecular meshwork and mild rubeosis iridis, but the neovascularization of the angle could not be clearly confirmed due to the presence of so many crystals. Pars plana vitrectomy was performed to remove clusters of crystals and bevacizumab was injected intravitreally to treat iris neovascularization. Aqueous aspirate was examined by light microscopy and the typical highly refringent cholesterol crystals were identified. Intraocular pressure returned to a normal level after the bevacizumab injection, although severe cholesterosis was still evident in the anterior chamber. To our knowledge, this would be the first Korean case of cholesterosis bulbi combined with chronic retinal detachment and presumed neovascular glaucoma, which was treated by pars plana vitrectomy and intravitreal bevacizumab injection.

The clinicopathological data of 1146 enucleated eyes obtained from 1146 patients (485 females and 661 males; mean age 57.4 (SD 21.6) years) between 1980 and 1990 were reviewed. The most common underlying diseases included trauma (37.4%), malignant tumours (19.6%), systemic diseases (diabetes, vascular diseases) (17.1%), surgical diseases (retinal detachment, glaucoma, cataract, corneal dystrophy) (14.1%), infection and inflammation (7%). The most frequent indications for enucleation were secondary angle closure glaucoma (34.9%), ocular malignant tumours (21.7%), atrophia or phthisis bulbi (18.7%), ocular infectious or inflammatory disease (14.7%), and recent trauma (enucleation was performed within the first month after trauma) (11.2%). Histopathologically, diagnoses included secondary angle closure (691 eyes or 60.3%), rubeosis iridis (550 or 48%), endothelialisation of the iridocorneal angle (198 or 17.3%), and retrocorneal membrane (143 or 12.5%). These data indicate that rubeosis iridis, often followed by irreversible secondary angle closure, represents the most common pathogenetic reason for enucleating eyes. Management procedures must be directed towards the prevention or consequent therapy of rubeosis iridis.