Kerala Journal of Ophthalmology

: 2018  |  Volume : 30  |  Issue : 3  |  Page : 219--221

Journal Review

Neeta Sidhan 
 Assistant Professor,Department of Ophthalmology, Regional Institute of Ophthalmology, Thiruvananthapuram, Kerala, India

Correspondence Address:
Neeta Sidhan
Assistant Professor,Department of Ophthalmology, Regional Institute of Ophthalmology, Thiruvananthapuram, Kerala

How to cite this article:
Sidhan N. Journal Review.Kerala J Ophthalmol 2018;30:219-221

How to cite this URL:
Sidhan N. Journal Review. Kerala J Ophthalmol [serial online] 2018 [cited 2022 Dec 2 ];30:219-221
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 The Impact of Chronic Use of Prostaglandin Analogs on the Biomechanical Properties of the Cornea in Patients with Primary Open-Angle Glaucoma

Meda R et al. Br J Ophthalmology 2017;101:120-5.

Corneal biomechanics has incited much interest in recent years for its implication in glaucoma, although its exact relationship is not entirely understood. The ocular response Analyzer (ORA; Reichert, New York, USA), a nontouch tonometer provides intraocular pressure (IOP) readings adjusted for corneal biomechanics, as well as quantifiable viscoelastic parameters of the cornea, namely, corneal hysteresis (CH) and corneal resistance factor (CRF).

The biomechanics of the peripapillary sclera and lamina cribosa have been well established to play a crucial role in glaucoma pathogenesis. The scleral canal, the sole opening in a pressurized globe, is a major stress-bearing area with experimental murine models having shown that strains with stiffer sclera provide greater resistance to deformation and are less susceptible to glaucomatous damage. The cornea being in continuity with the posterior scleral wall, it has therefore been speculated that CH serves as a surrogate measure of the ability of the posterior segment in withstanding stress. In a prospective study by Wells et al., where transient IOP elevation was induced in normal patients and patients with glaucoma, a significant correlation between CH and optic nerve surface deformation was found only in glaucomatous eyes. Patients with glaucoma have been found to have lower CH than normal patients and those with ocular hypertension. A low CH has also been associated with advanced glaucoma damage and glaucoma progression. Moreover, several studies have demonstrated recovery of CH following surgical or medical treatment for glaucoma. Since IOP remains the most important modifiable risk factor in the treatment of glaucoma, the accuracy of its measurement carries significant clinical impact in the management of galucoma.

The effect of chronic use of topical prostaglandin analogs (PGAs) on corneal biomechanical properties and measurement of IOP in eyes with primary open-angle glaucoma (POAG) was studied in this prospective, interventional case-control study from Montreal Glaucoma Institute, Canada. Seventy eyes from 35 patients with bilateral POAG on chronic PGA therapy of minimum 1-year duration was recruited. The study comprised three visits over 12 weeks. The better eye (study eye) per patient underwent PGA cessation for 6 weeks while the contralateral eye (control) continued to receive the treatment. Visit 2 took place 6 weeks after the PGA cessation. PGAs were then restarted in the study eyes, and all eyes were reassessed at the final visit 3. Corneal biomechanical properties, namely, CH, CRF and corneal-compensated IOP (IOPcc); IOP by Goldmann applanation (IOPGAT) and central corneal thickness (CCT) were measured at all visits. The discrepancy between IOPcc and IOPGAT was defined as IOP bias (IOPcc – IOPGAT).

In the study eyes, significant increases (P < 0.0001) were detected at visit 2 in CH (9.0 ± 1.8 vs. 10.3 ± 1.7 mm Hg), CRF (10.5 ± 2.1 vs. 11.7 ± 2.1 mm Hg), CCT (541.8 ± 43.2 vs. 551.9 ± 41.9 μm) and IOPGAT (15.4 ± 3.0 vs. 18.4 ± 3.8 mm Hg). IOP bias in this group was significantly lowered at visit 2 (P < 0.0001). These effects were reversed at visit 3. The control eyes did not demonstrate any significant changes over the study period. Cessation of chronic topical PGAs was hence found to be associated with significant increases in CH, CRF, and CCT, in addition to the expected elevation of IOP and reinitiation of the medication reversed these effects.

Topical PGAs lower IOP through increasing uveoscleral outflow while having minimal impact on the traditional trabecular outflow. Homeostasis of ciliary muscle and sclera extracellular matrix (ECM), which contain collagen types I, III, IV, laminin, and fibronectin, requires a fine balance between matrix metalloproteinases (MMP), that degrade specific proteins and the tissue inhibitors of matrix metalloproteinases (TIMP). PGAs have demonstrated to show significant MMP upregulation and TIMP downregulation with the corresponding altered gene expression in previous animal and human studies suggesting that PGAs stimulate ECM degradation of ocular surface tissue by modulating the balance between these enzymes. Studies in PGAs-treated rabbit eyes have also shown decreased collagen type I level and corneal thickness that corroborates the findings of this study. Few other studies, on the contrary, done in previously PGAs-naïve patients, showed an increase in CH within the first 6–12 months of therapy, paralleling IOP lowering. As IOP reduction by other topical hypotensive medications and by various surgical interventions results in CH recovery, it was hypothesized that the observed increase in CH in these studies might be largely due to IOP lowering, whereas the true effects of PGAs over corneal tissues remained camouflaged. This calls for additional caution when assessing the effectiveness of IOP lowering, especially in patients with more advanced glaucoma, which in itself tends to be associated with lower CH. The implication of the results hence warrant caution when clinicians assess the accuracy and adequacy of IOP control in patients under chronic PGAs therapy, especially in those with more advanced disease and lower CH.

 Five-Year Disease Progression of Patients Across the Glaucoma Spectrum Assessed by Structural and Functional Tools

Seth NG et al. Br J Opthalmology 2018;102:802-7.

In this study, adult glaucoma suspects and glaucoma patients, at the Glaucoma Clinic Advanced Eye Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, who underwent a baseline retinal nerve fiber layer (RNFL) thickness on spectral domain optical coherence tomography (SD-OCT) and reliable visual field (VF) tests on Humphrey field analyzer (HFA) prior to March 2010, were recruited for the study. Functional and structural progression of these patients over at least 5 years were compared using Glaucoma Progression Analysis (GPA) and VF index (VFI) on HFA and Guided Progression Analysis- OCT (GPA-OCT) on SD-OCT, respectively. Agreement of progression detection between the two modalities was computed using κ statistics.

The Guided Progression Algorithm (GPAOCT) compares RNFL thickness between the baseline and follow-up images and provides a topographical display of the area and location of significant change. Average thickness of the first two visits is taken as baseline. If the change on follow-up exceeds test–retest variability in one visit or two visits, the pixel is coded in yellow (possible loss) and in red (likely loss), respectively.

VF progression was defined using two analysis methods available on the HFA, namely, event-based analysis assessed by Glaucoma Progression Analysis (GPA) which represented the gold standard for progression in this study and trend-based analysis determined using VFI. The GPA compares the sensitivity values of individual points on follow-up VF with the sensitivity values of the same locations on an average of two baseline examinations. Progression was defined as a significant change detected in three points, and repeated at the same location in three consecutive follow-up tests, categorized by the GPA software as likely progression. The VFI quantifies perimetric rate of progression with VF. The rate of progression is calculated by linear regression analysis and presented as yearly change in the VFI.

One hundred and twenty-two patients (63 glaucoma suspects and 59 glaucoma patients) were included.

Among the 63 glaucoma suspects, 13 (20.6%) progressed to glaucoma by OCT and 9 (14.2%) using VF (seven on VFI; four on GPA). Two progressed by all three parameters, both of which showed progression by GPA-OCT first; predating VF progression by 11 months and 17 months, respectively. In glaucoma patients, GPA detected progression in five patients, VFI in six patients and GPA-OCT in six patients, with no patient progressing on all three GPA-OCT had poor agreement with GPA in glaucoma suspects (κ = 0.15; P = 0.13) and patients (κ = 0.10; P = 0.45). VFI had better agreement with GPA-OCT in glaucoma suspects (κ = 0.34; P = 0.01) than in glaucoma patients (κ = 0.12; P = 0.36). When compared with GPA, the sensitivity and specificity of GPA-OCT were 50% and 81.36%, respectively, in glaucoma suspects; whereas they were 20% and 90.74% in glaucoma patients.

Although studies have demonstrated good correlation between the global VF sensitivity and the peri-papillary RNFL thickness, the evidence is not as clear for progression on structural and functional testing. In this study, more patients among glaucoma suspects were labeled as “progressors to glaucoma” by SD-OCT than VF while among glaucoma patients, the number labeled “progressors” by VF and SD-OCT were nearly equal. In glaucoma suspects, earlier detection by OCT may be attributed to their younger age and hence thicker baseline RNFL which showed a faster decline. Similarly, Abe et al. had reported that progression in early disease was likely to be detected on SD-OCT, whereas progression in a more diseased eye was likely to be detected by standard automated perimetry. Shin et al., in their study, also recognized the limitation of using RNFL thickness as progression tools in eyes with advanced glaucoma, and reported ganglion cell-inner plexiform layer thickness as more useful for detecting structural progression because it is less likely to reach the measurement floor compared with RNFL thickness.

The study also attempted a novel technique to quantify RNFL loss in terms of the proportion lost from baseline rather than absolute values. Since the RNFL thickness in glaucoma patients is already attenuated at baseline, it is possible that the absolute decrease is not so apparent in spite of progression functionally. An interesting finding noted in the study was that the proportion of RNFL decline observed in progressors were similar in both suspects and glaucoma patients.

This study hence adds to the mounting evidence that structural change appears to be more useful to detect progression in glaucoma suspects, while functional change is a better indicator as the disease progresses. A better understanding and quantification of the relationship between structure and function is important since this would allow clinicians to tailor testing by one or the other method according to the stage of disease. Such a strategy could help maximize the chances of detecting progression while minimizing the costs associated with repeated testing.

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Conflicts of interest

There are no conflicts of interest.