Dear Editor

We thank Dr Ayata for the thoughtful comments of our article. He had three questions that we would like to answer as follows:
1) Figure 1 was quite important for the paper because it shows the exact location of the macular pigment in monkeys (courtesy of Francois Delori, PhD). We are sorry for the lack of the image in the on-line paper version but it was probably due to the PDF saving process.
2) We do not think there is any inconsistency between results and conclusion because that was exactly what we expected. If a pseudohole is a macular lesion where there is no loss of foveal tissue, the presence of foveal AF indicates the absence of macular pigment in the fovea. Being the pigment located in the outer plexiform layer and outer nuclear layer in the fovea (fig 1), that means we were dealing with lamellar rather than pseudo macular holes. Our paper just underlined the finding that OCT alone is inadequate to differentiate pseudo from lamellar holes. As to this respect AF imaging may be useful because reveals a loss of foveal tissue.
3) We are aware of the different aspects of AF-imaging after dark and light adaptation. As Dr Ayata properly pointed out, the visible changes in AF imaging in light and dark adapted eyes are minimal in the fovea and the lack of macular pigment in lamellar macular hole is in the fovea. The AF ratio was used to correlate AF intensities with residual retinal thickness at the bottom of the defect. The reason why we did not use raw images for AF quantitative measurements was related to the great difficulties in visualizing foveal defect in non normalized images. The ratio could have affected the results of these correlations but not the presence of foveal AF itself.

We thank again Dr Ayata for his interest in our article.

Ferdinando Bottoni ,MD

Dear Dr Radcliffe and colleagues,

Thank you for your comments. Two cases with the exfoliation syndrome and one with pigmentary glaucoma were included in our study. As you mentioned, dilatation of the pupil often causes a rise of intraocular pressure in such cases. However, none of the three individuals in our study had a significant rise of intraocular pressure or progression of glaucoma. Sincerely, George Spaeth M.D.

Dear Editor,

We read with great interest the recently published article by Bottoni and associates. However, we would like to express our concerns regarding their article entitled “Diagnosis of macular pseudoholes and lamellar macular holes: is optical coherence tomography the gold standard?” Br. J. Ophthalmol. published online 1 Feb 2008; doi:10.1136/bjo.2007.127597. [1] In this article, the authors investigate whether fundus autofluorescence imaging (FAF) differentiates between macular pseudo hole (MPH) and lamellar macular hole (LMH).

(First of all, figure 1 has not been presented. I guess it could be a technical error owing to the PDF rendering process).

Second, although corrected value of the foveal AF intensity was not found to be significantly different between the two groups (ie, pseudoholes and lamellar holes), authors concluded that AF imaging may add useful information as to the differential diagnosis of MPH from LMH. Moreover, they stated that the presence of foveal AF is consistent with a loss of foveal tissue and therefore a diagnosis of LMH. We believe there is an inconsistency between results and conclusion.

Third, several factors should be considered for evaluating FAF intensities in different examination and patient. Detector gain, pupillary alignment, refraction of the eye, lens status and number of the averaged image could be interfere pixel intensity of the FAF signal and those should be standardized before quantitative analyses of FAF images. [2] In the aforementioned article, standardization of the FAF images has not been clearly stated.

Ratio between the region of interest and background intensity appears reliable for single mean image quantification. However, bleaching of the photopigments due to the continuous visible light excitation may influence results and leads miscalculation. Bleaching with blue light is minimal at the fovea and is maximum approximately 12 degrees away from the fovea in the horizontal and vertical meridians. [3] Increment of the pixel intensity of the FAF image is depending on excitation time and amplitude of the fotobleaching is related amount of the photopigment and varies individually. According to our results (article in process), nearly 40% increment (range 18.8 % to 75.9 %) in FAF luminosity occurs during first thirty seconds of the excitation. For this reason, obtaining standard FAF images with accurate luminosity requires at least 30 second fundus illumination to bleach the photoreceptor pigments.

Considering these biasing factors (acquiring standardized FAF images, using accurate raw image processing algorithm) may provide more reliable results. Different analyse technics (i.e. circularity, eccentricity or transition pattern analyse) may grant the difference.

We thank Bottoni and his associates for their interesting article.

References

1. Bottoni F, Carmassi L, Cigada M, Moschini S, Bergamini F. Diagnosis of macular pseudoholes and lamellar macular holes: is optical coherence tomography the gold standard? Br J Ophthalmol. 2008 Feb 1; [Epub ahead of print] doi:10.1136/bjo.2007.127597

2. Schmitz-Valckenberg S, Holz FG, Fitzke FW. Perspectives in Imaging Technologies. In: Atlas of Fundus Autofluorescence Imaging, Holz FG, Spaide RF, Bird AC (editors). Springer – Verlag, Berlin 2007:325-34

3. Theelen T, Berendschot TT, Boon CJ, Hoyng CB, Klevering BJ. Analysis of visual pigment by fundus autofluorescence. Exp Eye Res. 2008;86:296-304.

Ali Ayata, MD ali_ayata@yahoo.com Gulhane Military Medical Academy Haydarpasa Training Hospital Department of Ophthalmology Istanbul-Turkey

Sinan Tatlipinar, Melih Unal, Dilaver Ersanli, Ahmet H Bilge Competing interest:None

Dear Editor,

We agree with the authors’ recommendation on the need for a sleep history in the eye clinic and probably having a lower threshold for referral to sleep physicians for further sleep studies.[1] However, we would like to bring to their attention other epidemiological studies where screening tools/sleep history have shown a high prevalence of sleep disorders in patients with ocular disorders other than non- arteritic anterior ischaemic optic neuropathy (NAION). These include primary open angle glaucoma (POAG), normal tension glaucoma (NTG), floppy eye lid syndrome (FES) and more recently central serous chorio-retinopathy (CSCR).[2-5] The evidence from these studies is summarized in table 1.

The literature shows a higher prevalence of sleep disorder than that reported in the general population in the United Kingdom by Ohayon et al (1.9% of population sample, n=4972) based on the minimal criteria of the International Classification of Sleep Disorders.[6]

We note the authors have adjusted the statistical analysis for glaucoma among other factors, but the proportion of patients diagnosed with glaucoma in the study and control groups is not mentioned. They also do not mention the ocular diagnosis of the randomly selected control group from the ophthalmology clinics and if any exclusion criteria, other than NAION was used. This may be the reason for their study having a lower proportion of patients with symptoms consistent with SAS than previously reported. The other reason can be the different screening methods used in these studies.

Also, the authors do not mention if the patients scoring positive on the Sleep Apnoea scale of the Sleep Disorders Questionnaire (SA-SDQ) were referred for sleep studies. Offering polysomnography or even limited sleep study to the study sample and comparing the outcomes with the SA-SDQ scores could provide the required evidence or validation, as mentioned by the authors, on the need for lower cut-off points for this patient sub-group.

We recently conducted a similar study in the general eye clinic population, which is under consideration for publication at the present time. Following a review of the various components of the screening questionnaire; patients with glaucoma were more likely to report episodes of apnoea, morning headaches, short term memory loss and poor concentration. We therefore suggest the authors also do a further analysis of the responses obtained to the 8 questions addressing the specific symptoms of SAS in the SA-SDQ, as they might be able to provide an additional weighted score for screening in their patient subgroup.

References

1. Li J, McGwin G, Vaphiades MS, Owsley C. Non-arteritic anterior ischaemic optic neuropathy and presumed sleep apnoea syndrome screened by the Sleep Apnoea scale of the Sleep disorders Questionnaire (SA-SDQ). Br J Ophthalmol 2007; 91:1524-1527.

2. Hakki Onen S, Mouriaux F, Berramdane L, Dascotte JC, Kulik JF, Rouland JF. High prevalence of sleep disordered breathing in patients with primary open angle glaucoma. Acta Ophthalmol Scand 2000; 78: 638-641.

3. Marcus DM, Costarides AP, Gokhale P, Papastergiou G, Miller JJ, Johnson MH, Choudhary BA. Sleep Disorders: A risk factor for normal tension glaucoma. J Glaucoma 2001; 10: 177-183.

4. McNab AA, The eye and sleep. Clinical Experimental Ophthalmology 2005; 33: 117-25.

5. Leveque TK, Yu L, Musch DC, Chervin RD, Zacks DN. Central serous chorioretinopathy and risk for obstructive sleep apnoea. Sleep Breath 2007; 11: 253-257.

6. Ohayon MM, Guilleminault C, Priest RG, Caulet M (1997) Snoring and breathing pauses during sleep: telephone interview survey of a United Kingdom population sample. BMJ, 314, 860–863.