**4. Detection of retinal nerve fibre layer defect and early diagnosis of glaucoma**

The diagnosis of glaucoma requires a confirmed glaucomatous VF defect that correlates with structural change. A glaucomatous visual field loss is defined as a cluster of ≥3 non-edged points in the PSD plot in a single hemifield with p value <5%, one of which must have a p value <1%; glaucoma hemifield test outside normal limits; and PSD with p value <5%. Any one of these criteria, if repeatable, was considered as sufficient evidence of a glaucomatous VF defect [27]. This has been considered as the gold standard of diagnosing glaucoma. OCT has gained popularity in the past decades and is now the standard for assessing structural damage of retinal nerve fibre layer (RNFL) and ONH for the detection of structural glaucomatous change. Indeed, RNFL and ONH measured by OCT were shown to be useful in differentiating normal eyes from even mild glaucoma [28]. Evidence suggests that RNFL thinning measured by OCT can detect glaucomatous damage several years before detectable functional deficits by VF testing [28–30]. The 10th World Glaucoma Association consensus meeting stated that 'detecting progressive glaucomatous RNFL thinning and neuroretinal rim narrowing is the best currently available gold standard for glaucoma diagnosis [31]'. This emphasised the importance of detecting RNFL abnormalities in terms of the diagnosis of glaucoma. Since OCT is becoming an invaluable tool for detecting early changes of ONH and RNFL thinning, especially because of its repeatability and objectiveness, it is logical to suggest that a risk scoring system for OHT patients should include OCT measurements.

On the contrary, the measurement of VCDR by stereoscopic photography or during clinical examination remains the only parameter in the risk calculator that reflects the structural status of the complex architecture of the ONH. During the slow and progressive process of glaucoma development, enlargement of VCDR could happen much later than the occurrence of RNFL thinning and other subtle structural glaucomatous damage. It is important to note that the powerful and carefully designed OHTS and EGPS were performed in the era when OCT was not widely used as an investigative tool. The two studies ruled out glaucoma patients from OHT mainly based on VF criteria and the absence of detectable structural damage on stereoscopic photography. Therefore, it might not be cavalier to suggest that a portion of these subjects might already have 'asymptomatic disease' (or preperimetric glaucoma) (**Figure 3**), and this damage was undetectable on stereoscopic photography, which was also suggested by Weinreb et al. [11]. The ever-evolving OCT technology and the concepts of ONH assessment can provide valuable data and new parameters for further refinement of the existing risk calculator, for instance, integrating other factors of OHN and RNFL based on OCT measurement [22]. The glaucoma risk model needs refinement that involves the advancing OCT technologies and concepts in measuring VCDR. Reliable risk estimation is

**125**

**trial**

*Risk Assessment of Ocular Hypertension and the Use of Medication*

both health economics and patients' quality of life.

*VF, visual field (adapted from Weinreb et al., 2004 [11]).*

**5.1 Detecting of RNFL thinning and disease progression**

may not replace GPA for topographic analysis of RNFL thinning.

**5.2 The dynamic target IOP, disease progression and quality of life: The LiGHT** 

Clinical trials usually define a treatment IOP-lowering target. For instance, the OHT study aimed for an IOP lowering by 20% from baseline for patients in the treatment arm [3], whereas the Collaborative Normal Tension Glaucoma (CNTG) study targeted an IOP lowering by 30% from baseline [42]. The Laser in Glaucoma

important as it may guide treatment decision, which in turn has consequences on

*Spectrum of disease in glaucoma. RNFL, retinal nerve fibre layer. OCT, optical coherence tomography.* 

**5. The new trends of early detection of glaucoma and disease progression**

Evidence shows that RNFL abnormalities can often be evident without detectable VF damage [32–35]. Therefore, measuring the change of RNFL is likely to be useful in detecting early disease progression. Spectral-domain OCT is now the invaluable investigation tool for glaucoma patients because it can measure RNFL thickness reliably [36] with high sensitivity and specificity to detect glaucoma [37, 38] and its progression [39]. Commercially available software event-based algorithm, such as the Guided Progression Analysis (GPA, Carl Zeiss Meditec), can detect progressive RNFL thinning using RNFL thickness maps. A study has demonstrated that GPA can detect and visualise different patterns of progressive RNFL thinning [39]. Trend-Based Progression Analysis (TPA) is another algorithm for detecting progressive RNFL thinning by measuring the rate of change in RNFL thickness for each superpixel of the RNFL thickness map (50 x 50 superpixels). A study that involved 139 POAG patients (240 eyes) followed up for ≥5 years showed that progressive RNFL thinning determined by GPA and TPA was predictive of detectable functional decline in glaucoma. The study showed that TPA outperformed GPA in detecting more eyes with progressive RNFL thinning at a similar level of specificity (84.2% vs. 81.7% for TPA and GPA, respectively) [40]. Furthermore, TPA also provides visualisation of the distribution of the rate of RNFL thinning. It was suggested that the detection of progressive RNFL loss can serve as a biomarker to reflect disease deterioration behaviour and hence guide glaucoma management [40]. However, TPA is not without its limitations. A minimum of four follow-up visits is required for the construction of the TPA, and performance can be undermined with fewer visits. In situations where there are abrupt RNFL changes or in eyes with large test-retest variability, the event-based analysis may be more useful [41]. The authors concluded that TPA enhances but

*DOI: http://dx.doi.org/10.5772/intechopen.90804*

**Figure 3.**

*Risk Assessment of Ocular Hypertension and the Use of Medication DOI: http://dx.doi.org/10.5772/intechopen.90804*

#### **Figure 3.**

*Visual Impairment and Blindness - What We Know and What We Have to Know*

risk of >15% (**Figure 2**). We should be careful when using the 5-year risk of >15% as our treatment threshold when using VCDR values that are obtained from different measurement techniques. This can dramatically alter the management approach for any OHT subjects, especially if they have a relatively high baseline estimated risk and/or larger VCDR. In the cohort of untreated OHT eyes from this study, up to 72 eyes (51.2%) would require treatment if OCT was used for assessing the VCDR, according to the ≥15% 5-year risk cut-off. On the other hand, only 54 eyes (38.6%) would require treatment if the VCDR measurements were obtained from stereophotography by one of the glaucoma specialists. Therefore, one must be cautious when applying the risk estimation obtained from the other means of measuring VCDR.

**4. Detection of retinal nerve fibre layer defect and early diagnosis of** 

The diagnosis of glaucoma requires a confirmed glaucomatous VF defect that correlates with structural change. A glaucomatous visual field loss is defined as a cluster of ≥3 non-edged points in the PSD plot in a single hemifield with p value <5%, one of which must have a p value <1%; glaucoma hemifield test outside normal limits; and PSD with p value <5%. Any one of these criteria, if repeatable, was considered as sufficient evidence of a glaucomatous VF defect [27]. This has been considered as the gold standard of diagnosing glaucoma. OCT has gained popularity in the past decades and is now the standard for assessing structural damage of retinal nerve fibre layer (RNFL) and ONH for the detection of structural glaucomatous change. Indeed, RNFL and ONH measured by OCT were shown to be useful in differentiating normal eyes from even mild glaucoma [28]. Evidence suggests that RNFL thinning measured by OCT can detect glaucomatous damage several years before detectable functional deficits by VF testing [28–30]. The 10th World Glaucoma Association consensus meeting stated that 'detecting progressive glaucomatous RNFL thinning and neuroretinal rim narrowing is the best currently available gold standard for glaucoma diagnosis [31]'. This emphasised the importance of detecting RNFL abnormalities in terms of the diagnosis of glaucoma. Since OCT is becoming an invaluable tool for detecting early changes of ONH and RNFL thinning, especially because of its repeatability and objectiveness, it is logical to suggest that a risk scoring system for OHT patients should include OCT measurements. On the contrary, the measurement of VCDR by stereoscopic photography or during clinical examination remains the only parameter in the risk calculator that reflects the structural status of the complex architecture of the ONH. During the slow and progressive process of glaucoma development, enlargement of VCDR could happen much later than the occurrence of RNFL thinning and other subtle structural glaucomatous damage. It is important to note that the powerful and carefully designed OHTS and EGPS were performed in the era when OCT was not widely used as an investigative tool. The two studies ruled out glaucoma patients from OHT mainly based on VF criteria and the absence of detectable structural damage on stereoscopic photography. Therefore, it might not be cavalier to suggest that a portion of these subjects might already have 'asymptomatic disease' (or preperimetric glaucoma) (**Figure 3**), and this damage was undetectable on stereoscopic photography, which was also suggested by Weinreb et al. [11]. The ever-evolving OCT technology and the concepts of ONH assessment can provide valuable data and new parameters for further refinement of the existing risk calculator, for instance, integrating other factors of OHN and RNFL based on OCT measurement [22]. The glaucoma risk model needs refinement that involves the advancing OCT technologies and concepts in measuring VCDR. Reliable risk estimation is

**124**

**glaucoma**

*Spectrum of disease in glaucoma. RNFL, retinal nerve fibre layer. OCT, optical coherence tomography. VF, visual field (adapted from Weinreb et al., 2004 [11]).*

important as it may guide treatment decision, which in turn has consequences on both health economics and patients' quality of life.
