Dear Editor,

We read with great interest, Singh et. al.’s[1] perspective on impression cytology and its uses in diagnosing ocular surface pathology. The known higher exposure to UV radiation in both Australia and New Zealand, and the increased incidence of ocular surface squamous neoplasia (OSSN) in Australia,[2][3] recently led us to audit the incidence of OSSN in conjunctival biopsies in New Zealand over a 6 year period.

We identified 132 invasive conjunctival and/or corneal biopsies performed on 115 patients at Auckland City Hospital. Among the many histopathological diagnoses, 6% of patients had no histological abnormality, questioning the need for an invasive diagnostic procedure. However, 62 (47%) biopsies were diagnosed with OSSN and 84% of those affected were men, with an average age of 72 years. Published recurrence rates are generally higher for more severe grades of OSSN[4] and four subjects in our audit eventually required an exenteration. Furthermore, of all biopsies on patients with OSSN, 27 biopsies had involvement of the margins and 12 patients required more than one surgical procedure. Two patients had recurrences even after clear margins at excisional biopsy and one patient had repeat biopsy, as there was clinical suspicion of recurrence but there was no histological evidence of further OSSN.

Although this disease is often regarded as a low grade malignancy affecting elderly men,[4] it is not without significant morbidity and occasionally mortality. However, these patients may not always be medically fit, have sufficiently healthy ocular surface for a large excision biopsy, or wish/consent to a biopsy.[5] Impression cytology may therefore offer an inexpensive, non-invasive tool that can be used in the outpatient clinic setting to help provide an objective evaluation of suspicious conjunctival/corneal lesions that enables patients to make more informed decisions about the need for surgery. Results of impression cytology may also help the ophthalmologist in forming the decision to perform an incisional or excisional biopsy and the necessity for any other associated procedures, such as freeze-thaw cryotherapy of the sclera/limbus and/or ethanol application to the cornea. Of course, the size of the lesion, macroscopic appearance and overall clinical opinion may still guide clinical decisions but impression cytology offers an additional confirmatory tool to aid the process. In addition, impression cytology can be used to monitor for recurrences in patients with previously treated OSSN in the outpatient setting.

Although impression cytology only allows sampling of the superficial cell layers,[1] the sensitivity of this technique has been documented at 70% when the lesion is found to be invasive by histology.[2] Consequently, some invasive lesions may still be missed. We anticipate that there are likely to be further improvements to the technique of impression cytology to make it more logistically simple and less time consuming, with perhaps an increase in sensitivity. In the meantime we agree that is a useful, often underused, complimentary investigation in the management of OSSN.

References

1 Singh R, Joseph A, Umapathy T, Tint NL, Dua HS. Impression cytology of the ocular surface. Br J Ophthalmol 2005;89:1655-9.

2 Nolan GR, Hirst LW, Bancroft BJ. The cytomorphology of ocular surface squamous neoplasia by using impression cytology. Cancer 2001;93:60-7.

3 Lee GA, Hirst LW. Retrospective study of ocular surface squamous neoplasia. Aust N Z J Ophthalmol 1997;25:269-76.

4 McKelvie PA, Daniell M, McNab A, Loughnan M, Santamaria JD. Squamous cell carcinoma of the conjunctiva: a series of 26 cases. Br J Ophthalmol 2002;86:168-73.

5 Tole DM, McKelvie PA, Daniell M. Reliability of impression cytology for the diagnosis of ocular surface squamous neoplasia employing the Biopore membrane. Br J Ophthalmol 2001;85:154-8.

Dear Editor:

We read with great interest the recent commentary by Stewart et al [1] describing the evidence of the blood flow disturbances in the pathogenesis of the glaucomatous damage. Although I agree with some of the findings of this excellent review, there are some important points that should be addressed:
1.After reading this article, one may think that there is not evidence that ocular blood flow abnormalities are involved in the pathogenesis of the glaucomatous damage. Different studies, using different devices, point in the same general direction indicating that on average blood flow is decreased in some glaucoma patients, especially in primary open-angle glaucoma (POAG) patients and in patients that progress despite normalized intraocular pressure (IOP) [2]. Furthermore this decrease in blood flow is not confined to the eye alone [3].
2. Many different methods are being used to measure directly or calculate indirectly in vivo ocular blood flow. Although there is not still a single method that can provide all the relevant information in one reading, the development of newer techniques and their corrected use provides the potential for assessing blood flow in humans.
3. On the other hand, the Authors reveal the lack of evidence of a pathogenic link between glaucoma and impaired ocular blood flow. They asked for a long-term prospective study, that includes carefully selected patient groups, with similar baseline demographic and clinical characteristics, but with dissimilar baseline ocular hemodynamics. We published a paper that prospectively investigated the value of color Doppler imaging of the ophthalmic artery and short posterior ciliary arteries in the prognosis of disease progression in patients with POAG. [4] When baseline demographic and clinical characteristics were stratified according to whether the eyes progressed during the 3-year follow-up period, the only parameters to show significant differences were the resistivity index of the ophthalmic artery and the resistivity index of the short posterior ciliary arteries. Our study concluded that poor blood flow in the retrobulbar vessels is closely linked to visual field deterioration in POAG patients.

In conclusion, we think that the understanding of the role of ocular blood flow disturbances in the pathogenesis of glaucoma has improved greatly. We have evidence that ocular blood flow is altered independently from IOP or level of damage in patients with progressive glaucoma, which could represent a primary risk factor for disease progression. In looking forward, we need long-term prospective multicenter studies to evaluate both the impact of ocular blood flow in glaucoma and the benefit of improving ocular blood flow.

References

1. Stewart WC, Feldman R, Mychaskiw MA. Ocular blood flow in glaucoma: the need for further clinical evidence and patient outcomes research. Br J Ophthalmol. 2007; 91: 1263-1264.

2. Flammer J., Orgül S., Costa VP., et al. The impact of ocular blood flow in glaucoma. Prog Retin Eye Res 2002; 21: 359-393.

3. Gasser P, Flammer J. Blood-cell velocity in the nailfold capillaries of patients with normal-tension and high-tension glaucoma. Am J Ophthalmol. 1991; 111: 585-588.

4. Martinez A, Sanchez M. Predictive Value of Color Doppler Imaging in a Prospective Study of Visual Field Progression in Primary Open-Angle Glaucoma. Acta Ophthalmol Scand 2005; 83: 716-723.

Dear Editor

We read with interest the editorial by Miller which comments on the paper, ‘Epidemiology of giant-cell arteritis in an Arab population: a 22-year study’[1]. The author of the editorial comments on geographical variation in the incidence of giant cell arteritis and cites evidence supporting both genetic and environmental aetiologies.

We re-examined the data from our 5 year study[2] looking at biopsy proven giant cell arteritis at Leicester Royal Infirmary and identified the ethnicity of the patients. This unit is the only tertiary ophthalmic referral centre for the county of Leicestershire, United Kingdom. Census data from 2001 indicates that ethnic Asians in Leicestershire make up 30% of the population. Out of a total of 42 biopsies, only 3 cases (7.1%) were from patients of Asian ethnicity. Whilst our study was not a prospective population based study, the data lends weight to the idea that GCA is relatively rare in ethnic Asians.

Interestingly our findings differ from those of Lam et al[3] who found the prevalence of GCA to be similar in Hispanic and non-Hispanic patients. Inferences can be made about the aetiology of a disease by examining the incidence of a disease in migrant populations when the direction of migration is from an area of low incidence to an area of high incidence. For example, the incidence of multiple sclerosis in Indian and Pakistani migrants to the UK has been studied[4] and it has been found that migration prior to the age of 15 years confers an increased risk of developing multiple sclerosis, a finding which implicates environmental agents. Similar prospective studies looking at the relationship between age at migration and risk of developing GCA may yield more information about the interplay between genetic and environmental factors.

References

1. Miller NR. Epidemiology of giant cell arteritis in an Arab population: a 22-year study. Br J Ophthalmol. 2007 Jun;91(6):705-6.

2. Jain S, Shah A, Deane J. Giant cell arteritis. (letter). Ophthalmology. 2007 Jun;114(6):1235

3. Lam BL, Wirthlin RS, Gonzalez A, Dubovy SR, Feuer WJ. Giant cell arteritis among Hispanic Americans. Am J Ophthalmol. 2007 Jan;143(1):161-3

4. Dean G, Elian M. Age at immigration to England of Asian and Caribbean immigrants and the risk of developing multiple sclerosis. J Neurol. Neurosurg. Psychiatry 1997;63:565-568

Re: van Leeuwen R, Eijkemans MJC, Vingerling JR, Hofman A, de Jong PTVM, Simonsz HJ Risk of bilateral visual impairment in individuals with amblyopia: the Rotterdam study BJO 2007;91 (11): 1450

Josefin Nilsson The negative impact of amblyopia from a population perspective: untreated amblyopia almost doubles the lifetime risk of bilateral visual impairment. BJO 2007;91 (11): 1417

Dear Editor

It is not surprising that amblyopes are at higher risk of bilateral visual impairment since impaired visual functions of the fellow eye have been previously demonstrated. Leguire et al warned that “In future studies of amblyopia, whether in children or in adults, caution is advised in assuming that the nonamblyopic eye is normal because acuity is normal.” [2] Johnson found that both amblyopic and fellow eyes had central scotomata, even after apparently successful treatment, [3] and concluded that “ocular effects of amblyopia may not be strictly limited to the amblyopic eye.” [4] Anomalous optic discs, reduced axial lengths,[5] and anatomic abnormalities involving the axial length to optic disc area have been reported as present to different degrees in amblyopic and fellow eyes.[6,7] Moreover, amblyopia is commonly associated with systemic disorders such as prematurity and low birth weight[8] even in the absence of retinopathy. [9] These anatomic and functional factors put both eyes at risk makes them more susceptible to vision loss.

Nilsson’s editorial implies that lack of screening and treatment of amblyopia cause a lifelong handicap[10] and that treatment offer a significant cost / benefit gain.[11,12] These beliefs employed several unsupported assumptions. Among them is that treatment results in final visual acuity sufficient to perform all tasks and that untreated amblyopia has a financial handicap equivalent to workman’s compensation scales for loss of an eye. Actually, treatment of severe amblyopia rarely results in functionally useful vision.[13] PEDIG studies showed that approximately 25 percent of their treated patients had no or very limited improvement at the end of their initial observation period.[14,15] Initial successes were reduced by an anticipated 50 percent rate of recidivism.[16,17] Furthermore, the assumption that improved Snellen acuity reflects functional improvement is challenged by findings that reading speed is significantly less than normal even when final acuity was comparable with the controls. [18]

A retrospective demographic investigation concluded that “No functionally or clinically significant differences existed between people with and without amblyopia in educational outcomes, behavioral difficulties or social maladjustment, participation in social activities, unintended injuries (school, workplace, or road traffic accidents as driver), general or mental health and mortality, paid employment, or occupation based social class trajectories.”[19]

There is an absolute need for effective allocation of medical resources.[20] Increased bilateral vision impairment among people with initial anatomic ocular defects in both eyes must motivate efforts to prevent those prenatal conditions leading to impaired ocular anatomy.

Respectfully submitted, Philip Lempert, MD

References

1. van Leeuwen R, Eijkemans MJC, Vingerling JR, Hofman A, de Jong PTVM, Simonsz HJ Risk of bilateral visual impairment in individuals with amblyopia: the Rotterdam study BJO 2007;91 (11): 1450
2. Leguire LE, Rogers GL, Bremer DL Amblyopia: the normal eye is not normal. J Pediatr Ophthalmol Strabismus 1990;27(1):32-38
3. Johnson DA Relative scotomata in the "normal" eye of functionally patients. A scanning laser ophthalmoscope (SLO) micreperimetric study. Binocul Vis Strabismus Q. 2007;22(1):17-48.
4. Johnson DA The use of the scanning laser ophthalmoscope in the evaluation of amblyopia (an American Ophthalmological Society thesis). Trans Am Ophthalmol Soc. 2006;104:414-36.
5. Lempert P. Porter L. Dysversion of the optic disc and axial length measurements in a presumed amblyopic population J Amer Acad Ped Ophthalmol Strabismus 1998;2:207-213
6. Lempert P. Axial length – disc area ratio in esotropic amblyopia. Arch Ophthalmol 2003; 121:821-824
7. Lempert P The axial length / disc area ratio in anisometropic hyperopic amblyopia: A hypothesis for decreased unilateral vision associated with hyperopic anisometropia. Ophthalmology 2004:111:304-308
8. Holmström G, M el Azazi M, Kugelberg U Ophthalmological follow up of preterm infants: a population based, prospective study of visual acuity and strabismus Br J Ophthalmol 1999;83:143-150
9. O’Connor AR, Stephenson TJ, Johnson A, Tobin MJ, Ratib S, Moseley M, Fielder AR Visual function in low birthweight children . British Journal of Ophthalmology 2004: 88 (9): 1149 - 1153
10. Josefin Nilsson The negative impact of amblyopia from a population perspective: untreated amblyopia almost doubles the lifetime risk of bilateral visual impairment. BJO 2007;91 (11): 1417
11. Joish VN, Malone DC, Miller JM. A cost-benefit analysis of vision screening methods for preschoolers and school-age children. J AAPOS 2003;7:283-290
12. Membreno JH, Brown MM, Brown GC, Sharma S, Beauchamp GR. A cost- utility analysis of therapy for amblyopia.Ophthalmology. 2002;109(12):2265 -2271.
13. Ingram RM Amblyopia: the need for a new approach Brit J. Ophthalmol 1979:63:236-237
14. PEDIG A randomized trial of atropine vs. patching for treatment of moderate amblyopia in children. Arch Ophthalmol 2002;120:268-278
15. Pediatric Eye Disease Investigator Group. The course of moderate amblyopia treated with patching in children: experience of the amblyopia treatment study. Am J Ophthalmol. 2003;136(4):620-629
16. Simons K. Amblyopia characterization, treatment, and prophylaxis. Surv Ophthalmol. 2005;50(2):123-66
17. Rutstein RP, Fuhr PS Efficacy and stability of amblyopia therapy. Optom Vis Sci 1992;69(10):747-754
18.Stifter E, Burggasser G, Hirmann E, Thaler A, Radner W. Monocular and binocular reading performance in children with microstrabismic amblyopia. Br J Ophthalmol. 2005;89(10):1324-9
19. J S Rahi, P M Cumberland, and C S Peckham Does amblyopia affect educational, health, and social outcomes? Findings from 1958 British birth cohort BMJ 2006; 332: 820-825
20. Woolf SH Potential Health and Economic Consequences of Misplaced Priorities. JAMA 2007;197(5) 523-526