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Pharma June 2011 Cover Figure 1A. Matrix 24-2 test results (left eye) Figure 1B. Matrix 24-2 test results (right eye) Figure 2A. Optic nerve head photograph (right eye) Figure 2B. Optic nerve head photograph (left eye) Figure 3. HRT results Figure 4. Zeiss Cirrus OCT results Figure 5. GDx PRO results Figure 6A. HRT trend analysis (right eye) Figure 6B. HRT trend analysis (left eye)

As featured in the June edition of Pharma.

A 53-year-old Asian female was referred to the Centre for Eye Health (CFEH) for a glaucoma assessment as a result of a significant family history of glaucoma (including father, paternal aunt and paternal uncle). Her ocular history also included blunt trauma to both eyes from a car accident 15 years earlier resulting in an inferior orbital wall blow-out fracture to the right eye (surgically repaired), and a permanent ecchymosis of the left superior eyelid. The client’s glaucoma risk profile also included myopia, with the left eye having a significantly higher refractive error than the right eye.  

Monitored closely over previous years, her Humphrey visual fields were consistently clear. A recent Matrix FDT, however, showed a possible inferior nasal arcuate defect in the right eye, and a superior nasal step in the left eye, prompting referral to CFEH for further investigation. 

Upon examination by clinical staff at the Centre, the client's pupil reactions were normal, and gonioscopy showed angles open to the ciliary body in all sectors and inferior angle recession in both eyes. Intraocular pressures (IOP) were 16.5mmHg in the right eye and 16mmHg in the left eye at 11am. Pentacam imaging showed regular corneal topography, and pachymetry in the centre of the pupil was 516µm in the right eye and 527µm in the left eye.

A repeat Matrix assessment (Figure 1) was essentially clear for the right eye but, consistent with the previous result, showed a superior nasal step in the left eye.

Funduscopy, HRT3 Moorfields Regression Analysis, GDx Pro and Cirrus Optical Coherence Topography (OCT) scans were performed (Figures 2-5).  The results collectively showed:

• Glial tissue inferiorly on the right optic nerve head, with mild beta peripapillary atrophy (PPA) temporal to the left eye;
• A notch in the inferior neuro-retinal rim (NRR) of the left eye, with an associated thinning of the retinal nerve fibre layer (RNFL);
• A sloped and relatively thin superior NRR in both eyes, with a relative reduction of the superior RNFL in the right eye.

The structural and functional assessments correlated well, suggesting glaucomatous damage to the left neural tissue with a probable angle recession component. 

It is thought that IOP elevation with angle recession is secondary to trabecular meshwork damage, rather than as a direct result of the recession itself (1).

Approximately 6-9% of clients develop glaucoma within 10 years of developing angle recession (1), and the risk is proportionate to the extent of angle recession.

The client was referred for ophthalmological assessment, and Selective Laser Trabeculoplasty (SLT) was subsequently performed on the left eye. SLT utilises a double frequency Nd:YAG laser and a green wavelength light (532nm). The pulse duration is limited to three nanoseconds and fixed at 400µm in diameter (2). The most commonly accepted theory is that the SLT mechanism releases cytokines, stimulating macrophage recruitment, to remodel the extracellular matrix of the trabecular meshwork (3).

The SLT technique has been shown to cause minimal mechanical damage to the trabecular meshwork, as opposed to coagulative necrosis resulting from Argon Laser Trabeculoplasty (ALT) (4).

Studies have shown that ALT treatment for angle recession glaucoma is ineffective (5), although no studies on the effectiveness of SLT in angle recession were found. Given this particular client's historical risk profile, it is likely that the angle recession is only one component of her optic neuropathy.  A recent 12 month retrospective study showed that SLT effectively controlled IOP in normal tension glaucoma (6). As a result, and given the client’s relatively young age, SLT was selected in an attempt to minimise their long term dependence on topical medication. The treating ophthalmologist reported a 25% reduction in IOP after performing SLT on the left eye.

The client returned to CFEH for repeat imaging 12 months after the SLT and subsequent follow-up. IOPs measured 16mmHg in the right eye and 15mmHg in the left eye. The GDx Pro, Cirrus OCT and topographical change analysis available with the HRT3 all require a minimum of at least three examinations to produce a change analysis so it is difficult to distinguish instrument variability from real change at a second visit. However, stereometric parameter analysis with the HRT3 can be calculated after two visits, and in this case the results suggested a slight decrease in the right eye but a slight increase in the left eye (Figure 6). While this result is most likely due to inter-test reliability of the instrument, there is published evidence of reversed cupping after reduced  IOP (7, 8, 9).  A third assessment will be needed to further document and establish any changes.

Conclusion
Glaucoma is a complex condition with multiple aetiologies and associations. A definitive cause is proving elusive for the condition in general, and also with individual cases such as this.  Whilst stereoscopic evaluation of the optic nerve is still considered the gold standard for assessing the neuro-retinal rim, imaging devices, such as those available at CFEH, can provide additional information to not only assist with the initial diagnosis, but for monitoring subsequent changes.

References

1. Kanski, J. Clincial Ophthalmology 6^th Ed. Butterworth Heinemann 2007, Pg 410 – 411.
2. http://www.ophthalmic.lumenis.com
   /slt_how.
3. Latina MA, DeLeon JM. Selective laser trabeculoplasty. Ophthalmol Clin N Am 2005; 18:409–419.
4. Kramer TR, Noecker RJ. Comparison of the morphologic changes after selective laser trabeculoplasty and argon laser trabeculoplasty in human eye bank eyes. Ophthalmology 2001; 108:773–779. 
5. Robin AL, Pollack IP, Argon Laser Trabeculoplasty in Secondary Forms of Open-Angle Glaucoma         Arch Ophthalmol. 1983;101(3):382-384.
6. El Mallah MK, Walsh MM, Stinnett SS, Asrani SG, Selective laser trabeculoplasty reduces mean IOP and IOP variation in normal tension glaucoma patients.  Clin Ophthalmol. 2010; 4: 889–893.
7. Yuen D, Buys Y. Disc photography and Heidelberg retinal tomography documentation of reversal of cupping following trabeculectomy. Graefes Arch Clin Exp Ophthalmol 2010; 248:1671-1673.
8. Katz LJ, Spaeth GL, Cantor LB, Poryzees EM, Seinmann WC. Reversible optic disc cupping and visual field improvement in adults with glaucoma. Am J Ophthalmol 1989; 107:485-492.
9. Harju M, Saari J, Kurvinen L, Vesti E. Reversal of optic disc cupping in glaucoma. Br J Ophthalmol Jul 2008; 92(7):901-905.