Thank you for raising the issue of abbreviations entering the virological lexicon which might give rise to confusion and misunderstanding. Over a decade has elapsed since our patient report was published and the source material is not retrievable. However, our recollection is the patient was discussed contemporaneously at the MDT and the viral aetiology, radiology findings and medical management determined and documented, from which the data was sourced for the 2008 report. Plausible as it may seem, it is not possible to test the veracity of the suggestion that the names ‘Jamestown Canyon’ and ‘John Cunningham’ might have been transposed during that MDT many years after the event, paper records are not kept indefinitely in NHS practice and ethics in medical publishing demands that patient identifiers are not described or retained in order to preserve anonymity. Perhaps the latter should have been considered over half a century ago when JC virus was first identified in the brain of the unfortunate patient after whom the eponymous pathogen was christened
(Padgett BL, Walker DL; et al. (1971). "Cultivation of papova-like virus from human brain with progressive multifocal leucoencephalopathy". Lancet. 1 (7712):
1257–60. doi:10.1016/S0140-6736(71)91777-6)
I read with interest the article by Jonas et al 1. The main purpose of the authors was to explore associations between a disc size change and other morphological parameters. Indeed, many non-ophthalmic and game-changing parameters are associated with disc size change and other morphological parameters, such as the serum lipids 2 dietary factors (such as lutein, zeaxanthin, and omega-3 fatty acids) 2-4, medications (such as lipid-lowering agents) 2, genetic susceptibility, body mass index, age and sex 3, among which only age and sex are addressed in their retrospective analysis.
According to the authors, decrease in the ophthalmoscopic disc size in the myopic eyes during the 10-year follow up, is likely related to a shift of the Bruch’s membrane opening as the inner of the three optic nerve head canal layers into the direction of the fovea. While their interpretations can be partly true, their attributed mechanism is subject to many biases.
Firstly, changes in ophthalmoscopical optic disc size and Bruch’s membrane are a function of macular pigment optical density 5-7, which in turn is a function of dietary carotenoid intake 8;9. Tong et al 10 have shown before that macular pigment optical density (MPOD) is inversely associated with axial length in Chinese subjects with myopia, suggesting that carotenoid intake, particularly lutein, is associated to axial length as well. Another study with a smaller sample size (45 eyes of 32 patients) with a different mean a...
I read with interest the article by Jonas et al 1. The main purpose of the authors was to explore associations between a disc size change and other morphological parameters. Indeed, many non-ophthalmic and game-changing parameters are associated with disc size change and other morphological parameters, such as the serum lipids 2 dietary factors (such as lutein, zeaxanthin, and omega-3 fatty acids) 2-4, medications (such as lipid-lowering agents) 2, genetic susceptibility, body mass index, age and sex 3, among which only age and sex are addressed in their retrospective analysis.
According to the authors, decrease in the ophthalmoscopic disc size in the myopic eyes during the 10-year follow up, is likely related to a shift of the Bruch’s membrane opening as the inner of the three optic nerve head canal layers into the direction of the fovea. While their interpretations can be partly true, their attributed mechanism is subject to many biases.
Firstly, changes in ophthalmoscopical optic disc size and Bruch’s membrane are a function of macular pigment optical density 5-7, which in turn is a function of dietary carotenoid intake 8;9. Tong et al 10 have shown before that macular pigment optical density (MPOD) is inversely associated with axial length in Chinese subjects with myopia, suggesting that carotenoid intake, particularly lutein, is associated to axial length as well. Another study with a smaller sample size (45 eyes of 32 patients) with a different mean age did not show the same association 5. A detailed explanation of the reasons justifying these differences is provided elsewhere 11.
Secondly, in many medical situations (such as obesity, diabetes, etc.), MOPD is reduced dramatically 12;13. Jonas et al 1 report that only 89 highly myoptic eyes (i.e., 43.6%) were re-examined after 10 years. Although the authors report that the age of cases in 2011 did not differ significantly from the age of their controls in the survey of 2011, no other dietary or medical information is provided in their study. Thus, it is very difficult to draw a firm conclusion.
One can certainly question whether there were any changes in carotenoid intakes and/or any medical situation during a decade-long longitudinal study. In support of this argument, MOPD is reported to significantly increase within 3 months in healthy Japanese individuals supplemented with daily 10 mg of orally administered lutein or zeaxanthin 14. Interestingly, in high myopia, it has been shown that even after a shorter period of lutein supplementation (20 to 40 days), MPOD began to rise uniformly at an average rate of 1.13+/-0.12 milliabsorbance units/day. During this same period, the serum lutein concentration increased tenfold, and then approached a steady state plateau. Most critically, the optical density curve eventually levelled off some 40 to 50 days after the participants discontinued the supplement. Thus, even a modest period of dietary carotenoid intake may produce a 30 to 40% reduction in blue light reaching the photoreceptors, Bruch's membrane, and the retinal pigment epithelium 6.
Substantial differences are reported in terms of dietary carotenoid/lutein intake among Chinese population 15;16. This issue may be even more pronounced in a small sample size a low rate of re-participation.
We agree that geometrical reasons may lead to a decrease in the size of the ophthalmoscopically visible optic disc. However, their presumed mechanism 17 may simply be partially a byproduct of MOPD changes over time.
Reference List
1. Jonas JB, Zhang Q, Xu L et al. Change in the ophthalmoscopical optic disc size and shape in a 10-year follow-up: the Beijing Eye Study 2001-2011. Br.J Ophthalmol. 2021.
2. Renzi LM, Hammond BR, Jr., Dengler M et al. The relation between serum lipids and lutein and zeaxanthin in the serum and retina: results from cross-sectional, case-control and case study designs. Lipids Health Dis. 2012;11:33.
3. Bone RA, Landrum JT, Guerra LH et al. Lutein and zeaxanthin dietary supplements raise macular pigment density and serum concentrations of these carotenoids in humans. The Journal of nutrition 2003;133:992-8.
4. Lin KH, Tran T, Kim S et al. Advanced Retinal Imaging and Ocular Parameters of the Rhesus Macaque Eye. Transl.Vis.Sci Technol. 2021;10:7.
5. Benoudis L, Ingrand P, Jeau J et al. Relationships between macular pigment optical density and lacquer cracks in high myopia. J Fr.Ophtalmol. 2016;39:615-21.
6. Landrum JT, Bone RA, Joa H et al. A one year study of the macular pigment: the effect of 140 days of a lutein supplement. Exp.Eye Res. 1997;65:57-62.
7. Zarubina AV, Huisingh CE, Clark ME et al. Rod-Mediated Dark Adaptation and Macular Pigment Optical Density in Older Adults with Normal Maculas. Curr.Eye Res. 2018;43:913-20.
8. Ajana S, Weber D, Helmer C et al. Plasma Concentrations of Lutein and Zeaxanthin, Macular Pigment Optical Density, and Their Associations With Cognitive Performances Among Older Adults. Invest Ophthalmol.Vis.Sci 2018;59:1828-35.
9. Berendschot TT, Plat J, de JA et al. Long-term plant stanol and sterol ester-enriched functional food consumption, serum lutein/zeaxanthin concentration and macular pigment optical density. Br.J Nutr. 2009;101:1607-10.
10. Tong N, Zhang W, Zhang Z et al. Inverse relationship between macular pigment optical density and axial length in Chinese subjects with myopia. Graefes.Arch.Clin.Exp.Ophthalmol. 2013;251:1495-500.
11. Tong N, Zhang W, Wu X. Reply to the letter by Xing-Ru Zhang and Zhen-Yong Zhang: Comments on "Inverse relationship between macular pigment optical density and axial length in Chinese subjects with myopia". Graefes.Arch.Clin.Exp.Ophthalmol. 2013;251:2287.
12. Hammond BR, Jr., Ciulla TA, Snodderly DM. Macular pigment density is reduced in obese subjects. Invest Ophthalmol.Vis.Sci 2002;43:47-50.
13. Scanlon G, Connell P, Ratzlaff M et al. MACULAR PIGMENT OPTICAL DENSITY IS LOWER IN TYPE 2 DIABETES, COMPARED WITH TYPE 1 DIABETES AND NORMAL CONTROLS. Retina. 2015;35:1808-16.
14. Tanito M, Obana A, Gohto Y et al. Macular pigment density changes in Japanese individuals supplemented with lutein or zeaxanthin: quantification via resonance Raman spectrophotometry and autofluorescence imaging. Jpn.J Ophthalmol. 2012;56:488-96.
15. Ng ALK, Leung HH, Kawasaki R et al. Dietary habits, fatty acids and carotenoid levels are associated with neovascular age-related macular degeneration in Chinese. Nutrients 2019;11:1720.
16. Takata Y, Xiang YB, Yang G et al. Intakes of fruits, vegetables, and related vitamins and lung cancer risk: results from the Shanghai Men's Health Study (2002G_ô2009). Nutrition and cancer 2013;65:51-61.
17. Zhang Q, Xu L, Wei WB et al. Size and Shape of Bruch's Membrane Opening in Relationship to Axial Length, Gamma Zone, and Macular Bruch's Membrane Defects. Invest Ophthalmol.Vis.Sci 2019;60:2591-8.
In their 2008 case report, Muqit, et al. describe a case of “presumptive Jamestown Canyon viral retinitis.”1
Jamestown Canyon virus is a mosquito-borne, single-stranded, ribonucleic acid (RNA) orthobunyavirus that is endemic throughout much of North America.2,3 Infection with Jamestown Canyon virus may be asymptomatic or may result in a general febrile illness, meningitis, and/or meningoencephalitis.2,3 Beyond the above case report by Muqit, et al.,1 and another review article referencing this case report,4 Jamestown Canyon virus has not been reported to cause retinitis or other ocular manifestations.
Upon close review of the case report by Muqit, et al.,1 we believe the authors are likely describing a case of John Cunningham (JC) virus (a ubiquitous, double-stranded, deoxyribonucleic acid [DNA] human polyomavirus known to cause progressive multifocal leukoencephalopathy [PML] among the immunocompromised)5-7 rather than Jamestown Canyon virus.
First, the case patient with viral retinitis had underlying human immunodeficiency virus (HIV) infection and a low CD4 lymphocyte count (240 cells/mm3), making him immunocompromised and susceptible to reactivation of the John Cunningham (JC) virus. Second, the case patient had magnetic resonance imaging (MRI) brain findings (i.e., asymmetric, predominantly posterior, confluent, subcortical white matter hyperintensities involving U-fibers) that are classic for John Cunningham (JC) virus-related PML.6,7 In fact,...
In their 2008 case report, Muqit, et al. describe a case of “presumptive Jamestown Canyon viral retinitis.”1
Jamestown Canyon virus is a mosquito-borne, single-stranded, ribonucleic acid (RNA) orthobunyavirus that is endemic throughout much of North America.2,3 Infection with Jamestown Canyon virus may be asymptomatic or may result in a general febrile illness, meningitis, and/or meningoencephalitis.2,3 Beyond the above case report by Muqit, et al.,1 and another review article referencing this case report,4 Jamestown Canyon virus has not been reported to cause retinitis or other ocular manifestations.
Upon close review of the case report by Muqit, et al.,1 we believe the authors are likely describing a case of John Cunningham (JC) virus (a ubiquitous, double-stranded, deoxyribonucleic acid [DNA] human polyomavirus known to cause progressive multifocal leukoencephalopathy [PML] among the immunocompromised)5-7 rather than Jamestown Canyon virus.
First, the case patient with viral retinitis had underlying human immunodeficiency virus (HIV) infection and a low CD4 lymphocyte count (240 cells/mm3), making him immunocompromised and susceptible to reactivation of the John Cunningham (JC) virus. Second, the case patient had magnetic resonance imaging (MRI) brain findings (i.e., asymmetric, predominantly posterior, confluent, subcortical white matter hyperintensities involving U-fibers) that are classic for John Cunningham (JC) virus-related PML.6,7 In fact, the authors claimed that the MRI brain findings were “confirmatory of the underlying diagnosis.”1 No MRI brain findings are classic or confirmatory for Jamestown Canyon virus infection. Third, the case patient’s cerebrospinal fluid was reportedly positive for viral DNA by polymerase chain reaction. This could only be possible for a DNA virus (i.e., John Cunningham (JC) virus) and not an RNA virus (i.e., Jamestown Canyon virus). Fourth, recovery of John Cunningham (JC) viral nucleic acid from ocular tissues of HIV-infected patients has been previously reported, so there is already precedent for this virus to infect the eye.8 Finally, the case patient had no known travel to or any mosquito exposure in North America, where Jamestown Canyon virus is endemic.2,3
Given John Cunningham (JC) and Jamestown Canyon viruses have different virology, epidemiology, and clinical manifestations, we believe the viruses were mistaken for one another because they share the same first letters of their words (i.e., J and C) and their abbreviations were likely confused. If our suspicion is correct, this case report highlights the possible dangers of abbreviations in medicine and the need to clearly define potentially confusing abbreviations in medical literature.
References
1. Muqit MM, Devonport H, Smith RA, Dhillon B. Presumptive Jamestown Canyon viral retinitis. Br J Ophthalmol. 2008 Dec;92(12):1599-600, 1695-6. doi: 10.1136/bjo.2007.132902. PMID: 19029162.
2. Coleman KJ, Chauhan L, Piquet AL, Tyler KL, Pastula DM. An Overview of Jamestown Canyon Virus Disease. Neurohospitalist. 2021 Jul;11(3):277-278. doi: 10.1177/19418744211005948. Epub 2021 Mar 29. PMID: 34163560; PMCID: PMC8182404.
3. Pastula DM, Hoang Johnson DK, White JL, Dupuis AP 2nd, Fischer M, Staples JE. Jamestown Canyon Virus Disease in the United States-2000-2013. Am J Trop Med Hyg. 2015 Aug;93(2):384-9. doi: 10.4269/ajtmh.15-0196. Epub 2015 Jun 1. PMID: 26033022; PMCID: PMC4530766.
4. Karesh JW, Mazzoli RA, Heintz SK. Ocular Manifestations of Mosquito-Transmitted Diseases. Mil Med. 2018 Mar 1;183(suppl_1):450-458. doi: 10.1093/milmed/usx183. PMID: 29635625.
5. Padgett BL, Walker DL, ZuRhein GM, Eckroade RJ, Dessel BH. Cultivation of papova-like virus from human brain with progressive multifocal leucoencephalopathy. Lancet. 1971 Jun 19;1(7712):1257-60. doi: 10.1016/s0140-6736(71)91777-6. PMID: 4104715.
6. Grebenciucova E, Berger JR. Progressive Multifocal Leukoencephalopathy. Neurol Clin. 2018 Nov;36(4):739-750. doi: 10.1016/j.ncl.2018.06.002. PMID: 30366552.
7. Pinto M, Dobson S. BK and JC virus: a review. J Infect. 2014 Jan;68 Suppl 1:S2-8. doi: 10.1016/j.jinf.2013.09.009. Epub 2013 Oct 8. PMID: 24119828.
8. Eberwein P, Hansen LL, Agostini HT. Genotypes of JC virus, DNA of cytomegalovirus, and proviral DNA of human immunodeficiency virus in eyes of acquired immunodeficiency syndrome patients. J Neurovirol. 2005 Feb;11(1):58-65. doi: 10.1080/13550280590900391. PMID: 15804960.
We read with great interest the article by Forte et al1, "Swept source optical Coherence tomography Angiography in patients treated with hydroxychloroquine: co-relation of the functional and morphological test." Hydroxychloroquine (HCQ) is a widely used drug for the management of systemic lupus erythematosus and rheumatoid arthritis. Non-invasive tests like optical coherence tomography, optical coherence tomography-angiography, 10-2 visual fields and multifocal ERG (mf-ERG) help in the early detection of the toxicity.2 We would like to highlight here importance of adaptive optics, and various studies done for the early detection of HCQ toxicity. In the study by Forte et al, mf-ERG did not co-relate with the flow changes on OCT-A, however in another observation by Penrose et al (n=6) a depression of signals on multifocal ERG was found in the perifoveal region even when the patients had normal visual acuity and a normal fundus.3Costa et al found significant differences between the micro-perimetry in the patients taking hydroxychloroquine and controls.4 It will be interesting to know the authors take on this. Besides these, adaptive optics is emerging as an important tool to detect the early photo-receptor changes in patients with HCQ toxicity. Adaptive optics help in the direct visualization of the cone mosaic. Stepien et al in their observation on 4 patients observed that adaptive optics showed a loss of cone mosaic in the perifoveal region that corresponded with...
We read with great interest the article by Forte et al1, "Swept source optical Coherence tomography Angiography in patients treated with hydroxychloroquine: co-relation of the functional and morphological test." Hydroxychloroquine (HCQ) is a widely used drug for the management of systemic lupus erythematosus and rheumatoid arthritis. Non-invasive tests like optical coherence tomography, optical coherence tomography-angiography, 10-2 visual fields and multifocal ERG (mf-ERG) help in the early detection of the toxicity.2 We would like to highlight here importance of adaptive optics, and various studies done for the early detection of HCQ toxicity. In the study by Forte et al, mf-ERG did not co-relate with the flow changes on OCT-A, however in another observation by Penrose et al (n=6) a depression of signals on multifocal ERG was found in the perifoveal region even when the patients had normal visual acuity and a normal fundus.3Costa et al found significant differences between the micro-perimetry in the patients taking hydroxychloroquine and controls.4 It will be interesting to know the authors take on this. Besides these, adaptive optics is emerging as an important tool to detect the early photo-receptor changes in patients with HCQ toxicity. Adaptive optics help in the direct visualization of the cone mosaic. Stepien et al in their observation on 4 patients observed that adaptive optics showed a loss of cone mosaic in the perifoveal region that corresponded with the OCT findings. OCT findings in their study showed a loss of IS -OS junction with preservation of retinal pigment epithelium and external limiting membrane showing a "sinking hole defect". SD-OCT and adaptive optics also showed defects in the area which were unaffected on 10-2 perimetry, suggesting pre-clinical loss. 5 Similarly, Debellemanière G et al, in their study on eyes found that there was increased cone spacing and moderate cone loss with an increasing cumulative dose of HCQ.6 It will be interesting to know the author's point of view about this, Thus to conclude, the non-invasive investigations may aid in the early detection of HCQ toxicity.
References
1. Forte R, Haulani H, Dyrda A, et al
Swept source optical coherence tomography angiography in patients treated with hydroxychloroquine: correlation with morphological and functional tests. British Journal of Ophthalmology 2021;105:1297-1301.
2. Marmor MF, Kellner U, Lai TY, Melles RB, Mieler WF; American Academy of Ophthalmology. Recommendations on Screening for Chloroquine and Hydroxychloroquine Retinopathy (2016 Revision). Ophthalmology. 2016 Jun;123(6):1386-94
3. Penrose PJ, Tzekov RT, Sutter EE, Fu AD, Allen AW Jr, Fung WE, Oxford KW. Multifocal electroretinography evaluation for early detection of retinal dysfunction in patients taking hydroxychloroquine. Retina. 2003 Aug;23(4):503-12.
4. Martínez-Costa L, Victoria Ibañez M, Murcia-Bello C, Epifanio I, Verdejo-Gimeno C, Beltrán-Catalán E, Marco-Ventura P. Use of microperimetry to evaluate hydroxychloroquine and chloroquine retinal toxicity. Can J Ophthalmol. 2013 Oct;48(5):400-5. doi: 10.1016/j.jcjo.2013.03.018. PMID: 24093187.
5. Stepien KE, Han DP, Schell J, Godara P, Rha J, Carroll J. Spectral-domain optical coherence tomography and adaptive optics may detect hydroxychloroquine retinal toxicity before symptomatic vision loss. Trans Am Ophthalmol Soc. 2009 Dec;107:28-33. PMID: 20126479; PMCID: PMC2814561.
6. Debellemanière G, Flores M, Tumahai P, Meillat M, Bidaut Garnier M, Delbosc B, Saleh M. Assessment of parafoveal cone density in patients taking hydroxychloroquine in the absence of clinically documented retinal toxicity. Acta Ophthalmol. 2015 Nov;93(7):e534-40
Shang et al. conducted a prospective study to examine the effect of ophthalmic and systemic conditions on incident dementia (1). The adjusted hazard ratios (HRs) (95% confidence intervals [CIs]) of age-related macular degeneration (AMD), cataract, diabetes-related eye disease (DRED), and glaucoma at baseline for incident dementia were 1.26 (1.05 to 1.52), 1.11 (1.00 to 1.24), 1.61 (1.30 to 2.00), and 1.07 (0.92 to 1.25), respectively. Diabetes, heart disease, stroke and depression at baseline were also significantly associated with an increased risk of dementia. In addition, some combinations of ophthalmic and systemic conditions were at the higher risk for incident dementia. I have a comment about the study.
Vision impairment is a risk factor of dementia, and poor vision is independently associated with a decline in cognitive function (2). Shang et al. clarified that AMD, cataract, and DRED were risk of incident dementia, and some combinations with systemic conditions accelerated risk of incident dementia. Although glaucoma was not significantly associated with increased risk of al-cause dementia, it was significantly associated with increased risk of vascular dementia. The authors also conducted analysis by excluding data in the first 5 years of follow-up, consistent results were also specified on the combined effects of ophthalmic and systemic conditions on incident dementia. Although the mechanism of increased risk of dementia in combinations with ophthalmic and...
Shang et al. conducted a prospective study to examine the effect of ophthalmic and systemic conditions on incident dementia (1). The adjusted hazard ratios (HRs) (95% confidence intervals [CIs]) of age-related macular degeneration (AMD), cataract, diabetes-related eye disease (DRED), and glaucoma at baseline for incident dementia were 1.26 (1.05 to 1.52), 1.11 (1.00 to 1.24), 1.61 (1.30 to 2.00), and 1.07 (0.92 to 1.25), respectively. Diabetes, heart disease, stroke and depression at baseline were also significantly associated with an increased risk of dementia. In addition, some combinations of ophthalmic and systemic conditions were at the higher risk for incident dementia. I have a comment about the study.
Vision impairment is a risk factor of dementia, and poor vision is independently associated with a decline in cognitive function (2). Shang et al. clarified that AMD, cataract, and DRED were risk of incident dementia, and some combinations with systemic conditions accelerated risk of incident dementia. Although glaucoma was not significantly associated with increased risk of al-cause dementia, it was significantly associated with increased risk of vascular dementia. The authors also conducted analysis by excluding data in the first 5 years of follow-up, consistent results were also specified on the combined effects of ophthalmic and systemic conditions on incident dementia. Although the mechanism of increased risk of dementia in combinations with ophthalmic and systemic conditions might be difficult to be explained, medical care on both ophthalmic and systemic conditions will be indispensable to avid acceleration of cognitive decline.
References
1. Shang X, Zhu Z, Huang Y, et al. Associations of ophthalmic and systemic conditions with incident dementia in the UK Biobank. Br J Ophthalmol 2021 Sep 13. doi: 10.1136/bjophthalmol-2021-319508
2. Lim ZW, Chee ML, Soh ZD, et al. Association Between Visual Impairment and Decline in Cognitive Function in a Multiethnic Asian Population. JAMA Netw Open 2020;3(4):e203560.
We read with interest the recent publication by Bertolin et al. (“In vitro establishment, validation and characterisation of conjunctival epithelium outgrowth using tissue fragments and amniotic membrane”). Their validated conjunctival analogue of the simple limbal epithelial transplantation does represent a promising advance in the field. It is, however, interesting to note that the established tissue application was mainly validated on its growth potential and not specifically on its ability to reinstate a healthy ocular mucosal surface.
Functional validation is of utmost importance, especially as the glued fragments are directly transplanted. This approach circumvents the need for expensive cell culture but also bypasses the stringent release criteria for cell therapies or tissue-engineered transplantation products. We would suggest that before this technique can be considered fully validated, it should be demonstrated that the obtained conjunctival cells contribute to the first line of mucosal defence, i.e. barrier formation. Several conjunctival barriers can be identified, such as intercellular junction complexes, glycocalyx and secreted mucins. Bertolin et al. demonstrated the presence of tight junctions (cfr. ZO-1 protein) and a glycocalyx (cfr. membrane-associated mucin-1), but failed to address the presence of goblet cells. As goblet cells are responsible for the secretion of mucin 5AC, which is the most abundant mucin in the mucin la...
We read with interest the recent publication by Bertolin et al. (“In vitro establishment, validation and characterisation of conjunctival epithelium outgrowth using tissue fragments and amniotic membrane”). Their validated conjunctival analogue of the simple limbal epithelial transplantation does represent a promising advance in the field. It is, however, interesting to note that the established tissue application was mainly validated on its growth potential and not specifically on its ability to reinstate a healthy ocular mucosal surface.
Functional validation is of utmost importance, especially as the glued fragments are directly transplanted. This approach circumvents the need for expensive cell culture but also bypasses the stringent release criteria for cell therapies or tissue-engineered transplantation products. We would suggest that before this technique can be considered fully validated, it should be demonstrated that the obtained conjunctival cells contribute to the first line of mucosal defence, i.e. barrier formation. Several conjunctival barriers can be identified, such as intercellular junction complexes, glycocalyx and secreted mucins. Bertolin et al. demonstrated the presence of tight junctions (cfr. ZO-1 protein) and a glycocalyx (cfr. membrane-associated mucin-1), but failed to address the presence of goblet cells. As goblet cells are responsible for the secretion of mucin 5AC, which is the most abundant mucin in the mucin layer of the tear film, its presence is crucial to obtain a normal, hydrated ocular surface. Presence of mucin-producing goblet cells is so characteristic of the conjunctiva that it is a cardinal feature of impression cytology techniques in the diagnosis of corneal limbal stem cell deficiency. We therefore consider goblet cells (and their associated mucin production) in 2D and 3D cultures the “sine qua non” for conjunctival epithelium and propose that it should be a core element of the validated characterization process.
As functional goblet cells are difficult to maintain in culture, it could be debated that the absence of goblet cells in the outgrowth does not implicate their absence during in vivo expansion. If conjunctival stem cells in the outgrowth could be shown to have bipotent properties, it is reasonable to assume that conjunctival goblet cells can differentiate from these bipotent stem cells and that they can be preserved once they are placed in their natural tightly regulated environment, including the conjunctival innervation of the epithelium. Do the authors have any experience with goblet cell maturation? In any case, these properties would have to be well proven before this technique can be relied on in the clinic.
We like to congratulate Mullany et al. for their paper on normal-tension glaucoma is associated with cognitive impairment.1 To link normal-tension glaucoma (NTG) to cognitive impairment and therefore to a neurodegenerative process opens a new vista and research approach for glaucoma research. NTG indeed is an intriguing optic neuropathy that presents with a glaucomatous optic disc appearance and visual field loss similar to that seen in primary open angle glaucoma. The main risk factor for glaucoma however, increased intraocular pressure is missing.
Unlike other cranial nerves the optic nerve is a white matter tract of the brain, enveloped in the meninges (dura, arachnoid and pia mater) and surrounded by cerebrospinal fluid (CSF) on its entire length. And CSF indeed may be the link that connects the neurodegenerative process leading to cognitive impairment and the glaucomatous optic neuropathy in NTG. Recent research demonstrated a relationship between decreased CSF flow, measured in the ventricles and the spinal cord, and cognitive deficit in the elderly.2 In NTG, impaired CSF dynamics was demonstrated with computer assisted cisternography in the subarachnoid space of the intraorbital optic nerve most pronounced in the bulbar region behind the eye globe.3 In a recent publication we found an elevated L-PGDS concentration in the subarachnoid space of the optic nerve in NTG patients with optic nerve sheath compartment syndrome that results in a reduced CSF turnover.4...
We like to congratulate Mullany et al. for their paper on normal-tension glaucoma is associated with cognitive impairment.1 To link normal-tension glaucoma (NTG) to cognitive impairment and therefore to a neurodegenerative process opens a new vista and research approach for glaucoma research. NTG indeed is an intriguing optic neuropathy that presents with a glaucomatous optic disc appearance and visual field loss similar to that seen in primary open angle glaucoma. The main risk factor for glaucoma however, increased intraocular pressure is missing.
Unlike other cranial nerves the optic nerve is a white matter tract of the brain, enveloped in the meninges (dura, arachnoid and pia mater) and surrounded by cerebrospinal fluid (CSF) on its entire length. And CSF indeed may be the link that connects the neurodegenerative process leading to cognitive impairment and the glaucomatous optic neuropathy in NTG. Recent research demonstrated a relationship between decreased CSF flow, measured in the ventricles and the spinal cord, and cognitive deficit in the elderly.2 In NTG, impaired CSF dynamics was demonstrated with computer assisted cisternography in the subarachnoid space of the intraorbital optic nerve most pronounced in the bulbar region behind the eye globe.3 In a recent publication we found an elevated L-PGDS concentration in the subarachnoid space of the optic nerve in NTG patients with optic nerve sheath compartment syndrome that results in a reduced CSF turnover.4 Reduced CSF turnover is thought to result in malnutrition of axons, neurons and glial cells as well as in accumulation of toxic waste products on the other hand. An experimental induced optic nerve sheath compartment in an animal model demonstrated the most impressive damage to axons and glial cells not on the site where the compartment was created (close to optic canal), but behind the lamina cribrosa in an area densely packed with mitochondria.5 A toxic damage following the CSF compartmentation seems to be the most likely explanation.
We encourage to focus in further studies on CSF dynamics in both, dementia and NTG.
References:
1. Mullany S, Xiao L, Qassim A, Marshall H, Gharahkhani P, MacGregor S, Hassall MM, Siggs OM, Souzeau E, Craig JE. Normal-tension glaucoma is associated with cognitive impairment. Br J Ophthalmol. 2021 Mar 29:bjophthalmol-2020-317461. doi: 10.1136/bjophthalmol-2020-317461. Epub ahead of print. PMID: 33781990.
2. Attier-Zmudka J, Sérot JM, Valluy J, Saffarini M, Macaret AS, Diouf M, Dao S, Douadi Y, Malinowski KP, Balédent O. Decreased Cerebrospinal Fluid Flow Is Associated With Cognitive Deficit in Elderly Patients. Front Aging Neurosci. 2019 Apr 30;11:87. doi: 10.3389/fnagi.2019.00087. PMID: 31114494; PMCID: PMC6502902.
3. Pircher A, Montali M, Wostyn P, Pircher J, Berberat J, Remonda L, Killer HE. Impaired cerebrospinal fluid dynamics along the entire optic nerve in normal-tension glaucoma. Acta Ophthalmol. 2018 Aug;96(5):e562-e569. doi: 10.1111/aos.13647. Epub 2018 Mar 12. PMID: 29532640.
4. Pircher A, Neutzner A, Montali M, Huber A, Scholl HPN, Berberat J, Remonda L, Killer HE. Lipocalin-type Prostaglandin D Synthase Concentration Gradients in the Cerebrospinal Fluid in Normal-tension Glaucoma Patients with Optic Nerve Sheath Compartmentation. Eye Brain. 2021 Apr 14;13:89-97. doi: 10.2147/EB.S297274. PMID: 33883963; PMCID: PMC8053785.
5. Jaggi GP, Harlev M, Ziegler U, Dotan S, Miller NR, Killer HE. Cerebrospinal fluid segregation optic neuropathy: an experimental model and a hypothesis. Br J Ophthalmol. 2010 Aug;94(8):1088-93. doi: 10.1136/bjo.2009.171660. Epub 2010 May 27. PMID: 20508039
We would like to congratulate Uwaydat et al. on their large series of spontaneously closed macular holes (MH), which adds new information to the literature.(1) It reinforces the observation that traumatic MH can spontaneously close and that a period of observation in these eyes, where the results of surgery are not clear, is a worthwhile option. However, we disagree with their conclusion that eyes with recent onset small primary MHs should also be observed. The authors don’t suggest a time period for observation but found that the median time for closure for these small holes was 4.4 months.
The report by Uwaydat et al. has 40 authors and the 60 cases of idiopathic MH were collected over at least a two-year period. Assuming a conservative number of 25 MH cases seen per surgeon per annum, this would give a spontaneous closure rate of ~3%, which is similar to the published literature as the authors review in their article.
MH are known to enlarge with time, even in the short term. Madi et al, reported that 83% enlarged, by a median of 105 microns in 8 weeks. (2) Similarly, Berton et al recently estimated that holes less than 250 microns enlarge by a mean of 1.67 microns per day, resulting in a similar 100-micron increase in 2 months.(3)
The anatomical and visual outcomes of surgery are dependent on MH diameter and duration. Holes greater than 300 microns, and with a duration more than four months are less likely to regain 0.3 logMAR or better.(4)...
We would like to congratulate Uwaydat et al. on their large series of spontaneously closed macular holes (MH), which adds new information to the literature.(1) It reinforces the observation that traumatic MH can spontaneously close and that a period of observation in these eyes, where the results of surgery are not clear, is a worthwhile option. However, we disagree with their conclusion that eyes with recent onset small primary MHs should also be observed. The authors don’t suggest a time period for observation but found that the median time for closure for these small holes was 4.4 months.
The report by Uwaydat et al. has 40 authors and the 60 cases of idiopathic MH were collected over at least a two-year period. Assuming a conservative number of 25 MH cases seen per surgeon per annum, this would give a spontaneous closure rate of ~3%, which is similar to the published literature as the authors review in their article.
MH are known to enlarge with time, even in the short term. Madi et al, reported that 83% enlarged, by a median of 105 microns in 8 weeks. (2) Similarly, Berton et al recently estimated that holes less than 250 microns enlarge by a mean of 1.67 microns per day, resulting in a similar 100-micron increase in 2 months.(3)
The anatomical and visual outcomes of surgery are dependent on MH diameter and duration. Holes greater than 300 microns, and with a duration more than four months are less likely to regain 0.3 logMAR or better.(4)
Surgery achieves closure rates of over 98% for small and medium sized holes, and a risk of a worse visual outcome than preoperatively is very low.(4)
Taking this information together, observing a 200 micron hole with a 2-month duration, for even 2 months would likely result in a 100-micron size increase, and a four-fold reduction in the chances of achieving 0.3logMAR or better, set against a 5% chance of observing spontaneous closure.
The spontaneous closure rate in smaller holes is likely to be higher than previously stated however, it is not a common observation, and delaying surgery carries real risks for the patient. Although the options should be discussed with the patient, we advocate prompt surgery for all primary macular holes, including small ones, as the best means of achieving good functional results.
1. Uwaydat, S. H. et al. Clinical characteristics of full thickness macular holes that closed without surgery. Br. J. Ophthalmol. (2021) doi:10.1136/bjophthalmol-2021-319001.
2. Madi, H. A., Dinah, C., Rees, J. & Steel, D. H. W. The Case Mix of Patients Presenting with Full-Thickness Macular Holes and Progression before Surgery: Implications for Optimum Management. Ophthalmol. J. Int. d’ophtalmologie. Int. J. Ophthalmol. Zeitschrift fur Augenheilkd. 233, 216–221 (2015).
3. Berton, M., Robins, J., Frigo, A. C. & Wong, R. Rate of progression of idiopathic full-thickness macular holes before surgery. Eye (Lond). 34, 1386–1391 (2020).
4. Steel, D. H. et al. Factors affecting anatomical and visual outcome after macular hole surgery: findings from a large prospective UK cohort. Eye (Lond). 35, 316–325 (2021).
Atik et al (BJOhttps://bjo.bmj.com/content/105/5/602) have done an excellent job of summarizing the current state of the art for conducting health economic evaluations in ophthalmology. Not surprisingly, however, such tools and techniques were originally designed to address broader questions of healthcare funding and resource allocation across many disparate clinical areas. As such, the general use case was very far removed from ophthalmology. This is relevant as a central component is the calculation of the utility parameters used, particularly in cost-effectiveness calculations (1). At present, the standard default utility measure remains the EQ5D, which does not prima facie include a vision specific domain (2). Rather, a “Vision Bolt-On” to the EQ5D which asks patients whether they “Have no problems seeing”; “Have some problem seeing”; or “Have extreme problems seeing” is proposed for increasing the precision of the utility score derived from patients for ophthalmic interventions (3). Unfortunately, the “Vision Bolt On” while theoretically increasing the discriminating power of the EQ-5D has not been widely adopted in economic evaluations conducted in ophthalmology (3-4). Moreover, as currently configured, the “Vision Bolt On” questions fail to adequately account for the clinical differences, say between central or fine reading vision which may be more relevant in patients with age-related macular degeneration, versus...
Atik et al (BJOhttps://bjo.bmj.com/content/105/5/602) have done an excellent job of summarizing the current state of the art for conducting health economic evaluations in ophthalmology. Not surprisingly, however, such tools and techniques were originally designed to address broader questions of healthcare funding and resource allocation across many disparate clinical areas. As such, the general use case was very far removed from ophthalmology. This is relevant as a central component is the calculation of the utility parameters used, particularly in cost-effectiveness calculations (1). At present, the standard default utility measure remains the EQ5D, which does not prima facie include a vision specific domain (2). Rather, a “Vision Bolt-On” to the EQ5D which asks patients whether they “Have no problems seeing”; “Have some problem seeing”; or “Have extreme problems seeing” is proposed for increasing the precision of the utility score derived from patients for ophthalmic interventions (3). Unfortunately, the “Vision Bolt On” while theoretically increasing the discriminating power of the EQ-5D has not been widely adopted in economic evaluations conducted in ophthalmology (3-4). Moreover, as currently configured, the “Vision Bolt On” questions fail to adequately account for the clinical differences, say between central or fine reading vision which may be more relevant in patients with age-related macular degeneration, versus the loss of peripheral retinal photoreceptors on a patient’s navigation vision such as in glaucoma. Additional attempts designed to extend the “Vision Bolt On” including the Glaucoma Utility Index (GUI) to increase such discriminating abilities, however, have concluded that more research on the link between utility measures and precise clinical parameters is needed to better capture the subtle components of a patient’s vision on their overall global utility score (5). The time is, therefore, ripe for a concerted research effort to develop and validate such a truly relevant utility measure tailored to ophthalmic interventions.
Word Count: 300
References:
1. Smith AF, Brown GC. Understanding cost-effectiveness: a detailed review, Brit-J-Ophthalmol, 2000; 84: 794-798
3. Yang Y, Rowen D, Brazier J, et al. An exploratory study to test the impact on three "bolt-on" items to the EQ-5D. Value Health 2015 Jan;18(1):52-60.
4. Luo N, Wang X, Ang M, et al. A Vision "Bolt-On" Item Could Increase the Discriminatory Power of the EQ-5D Index Score. Value Health 2015;18(8):1037‐1042
5. Burr JM, Kilonzo M, Vale L, et al. Developing a preference-based Glaucoma Utility Index using a discrete choice experiment. Optom Vis Sci. 2007;84(8):797‐808
Martel et al. report the prevalence, features and risk factors of visual hallucinations following eye removal (1). The findings indicate that visual hallucinations may be a significant and prevalent association of eye amputation, occurring in around one-third of cases. Throughout the paper, visual hallucinations are referred to as phantom visions, and categorised under the broad catchment of the phantom eye syndrome that includes pain and tactile sensations as well as visual hallucinations. Although the authors speculate phantom visions could be considered a subtype of Charles Bonnet syndrome (CBS) they are reluctant to refer to them as CBS, perhaps because of the longstanding debate as to whether CBS should be used to refer to a specific type of visual hallucination or a specific underlying cause (2,3). Where CBS is used to refer to a specific hallucination type, it is typically reserved for complex hallucinations and excludes the simple, ‘elementary’ hallucinations described as the most common experiences following enucleation. The consequence is that a range of terms have evolved to describe symptoms that have the same cause, adding confusion to the literature and hindering research and extensive efforts to raise awareness and establish appropriate patient management pathways for people with visual hallucinations (4-6).
It is our opinion that both the simple and complex visual hallucinations described in the study should be referred to as Charles Bonnet syndrome....
Martel et al. report the prevalence, features and risk factors of visual hallucinations following eye removal (1). The findings indicate that visual hallucinations may be a significant and prevalent association of eye amputation, occurring in around one-third of cases. Throughout the paper, visual hallucinations are referred to as phantom visions, and categorised under the broad catchment of the phantom eye syndrome that includes pain and tactile sensations as well as visual hallucinations. Although the authors speculate phantom visions could be considered a subtype of Charles Bonnet syndrome (CBS) they are reluctant to refer to them as CBS, perhaps because of the longstanding debate as to whether CBS should be used to refer to a specific type of visual hallucination or a specific underlying cause (2,3). Where CBS is used to refer to a specific hallucination type, it is typically reserved for complex hallucinations and excludes the simple, ‘elementary’ hallucinations described as the most common experiences following enucleation. The consequence is that a range of terms have evolved to describe symptoms that have the same cause, adding confusion to the literature and hindering research and extensive efforts to raise awareness and establish appropriate patient management pathways for people with visual hallucinations (4-6).
It is our opinion that both the simple and complex visual hallucinations described in the study should be referred to as Charles Bonnet syndrome. In fact, irrespective of eye condition or visual pathway disease, surveys that include both simple and complex hallucinations find a similar ratio of simple to complex as that described by the authors following eye removal (see for example 7,8) and it has been argued previously that restriction of the use of CBS to denote complex hallucinations only should be revisited (3). Broadening the term to include simple and complex phenomena reflects current practice (9,10) and has become particularly pressing as the International Classification of Diseases (ICD-11) now includes CBS for the first time, using it to refer to the specific causal mechanism of visual release.
Inconsistent terminology in the visual hallucination literature threatens to widen the gap between patients and appropriate referral to support services. This problem is particularly acute in CBS due to low awareness of the condition among physicians (7, 11). There is need for unity to ensure all patients receive accurate and clear messaging about visual hallucinations and can be signposted to relevant organisations, such as Esme’s Umbrella, for advice and support.
References
1. Martel A, Baillif S, Thomas P, et al. Phantom vision after eye removal: prevalence, features and related risk factors. British Journal of Ophthalmology, Published Online First: 12 May 2021. doi: 10.1136/bjophthalmol-2021-319091
2. ffytche DH. Visual hallucinatory syndromes: past, present, and future. Dialogues in Clinical Neuroscience. 2007;9(2):173-189.
3. ffytche DH. Visual hallucinations and the Charles Bonnet syndrome. Current Psychiatry Reports. 2005;7(3): 168-79.
4. O'Brien J, Taylor JP, Ballard C, Barker RA, Bradley C, Burns A, Collerton D, Dave S, Dudley R, Francis P, Gibbons A. Visual hallucinations in neurological and ophthalmological disease: pathophysiology and management. Journal of Neurology, Neurosurgery & Psychiatry, 2020; 91(5): 512-519.
5. Carpenter K, Jolly JK, Bridge H. The elephant in the room: understanding the pathogenesis of Charles Bonnet syndrome. Ophthalmic and Physiological Optics, 2019; 39(6): 414-421.
6. Best J, Liu PY, ffytche D, Potts J, Moosajee M. Think sight loss, think Charles Bonnet syndrome. Therapeutic Advances in Ophthalmology, 2019. doi:10.1177/2515841419895909
7. Cox TM, ffytche DH. Negative outcome Charles Bonnet Syndrome, British Journal of Ophthalmology, 2014; 98: 1236-9.
8. Santhouse AM, Howard RJ, ffytche DH. Visual hallucinatory syndromes and the anatomy of the visual brain. Brain. 2000;123: 2055-64
9. Jones L, Moosajee M. Visual hallucinations and sight loss in children and young adults: a retrospective case series of Charles Bonnet syndrome. British Journal of Ophthalmology, Published Online First: 15 September 2020. doi: 10.1136/bjophthalmol-2020-317237
10. Jones L, Ditzel-Finn L, Potts J, Moosajee M. Exacerbation of visual hallucinations in Charles Bonnet syndrome due to the social implications of COVID-19. BMJ Open Ophthalmology, 2021; 6(1), p.e000670.
11. Gordon KD, Felfeli T. Family physician awareness of Charles Bonnet syndrome, Family Practice, 2018; 35(5): 595-8.
Thank you for raising the issue of abbreviations entering the virological lexicon which might give rise to confusion and misunderstanding. Over a decade has elapsed since our patient report was published and the source material is not retrievable. However, our recollection is the patient was discussed contemporaneously at the MDT and the viral aetiology, radiology findings and medical management determined and documented, from which the data was sourced for the 2008 report. Plausible as it may seem, it is not possible to test the veracity of the suggestion that the names ‘Jamestown Canyon’ and ‘John Cunningham’ might have been transposed during that MDT many years after the event, paper records are not kept indefinitely in NHS practice and ethics in medical publishing demands that patient identifiers are not described or retained in order to preserve anonymity. Perhaps the latter should have been considered over half a century ago when JC virus was first identified in the brain of the unfortunate patient after whom the eponymous pathogen was christened
(Padgett BL, Walker DL; et al. (1971). "Cultivation of papova-like virus from human brain with progressive multifocal leucoencephalopathy". Lancet. 1 (7712):
1257–60. doi:10.1016/S0140-6736(71)91777-6)
I read with interest the article by Jonas et al 1. The main purpose of the authors was to explore associations between a disc size change and other morphological parameters. Indeed, many non-ophthalmic and game-changing parameters are associated with disc size change and other morphological parameters, such as the serum lipids 2 dietary factors (such as lutein, zeaxanthin, and omega-3 fatty acids) 2-4, medications (such as lipid-lowering agents) 2, genetic susceptibility, body mass index, age and sex 3, among which only age and sex are addressed in their retrospective analysis.
According to the authors, decrease in the ophthalmoscopic disc size in the myopic eyes during the 10-year follow up, is likely related to a shift of the Bruch’s membrane opening as the inner of the three optic nerve head canal layers into the direction of the fovea. While their interpretations can be partly true, their attributed mechanism is subject to many biases.
Firstly, changes in ophthalmoscopical optic disc size and Bruch’s membrane are a function of macular pigment optical density 5-7, which in turn is a function of dietary carotenoid intake 8;9. Tong et al 10 have shown before that macular pigment optical density (MPOD) is inversely associated with axial length in Chinese subjects with myopia, suggesting that carotenoid intake, particularly lutein, is associated to axial length as well. Another study with a smaller sample size (45 eyes of 32 patients) with a different mean a...
Show MoreIn their 2008 case report, Muqit, et al. describe a case of “presumptive Jamestown Canyon viral retinitis.”1
Jamestown Canyon virus is a mosquito-borne, single-stranded, ribonucleic acid (RNA) orthobunyavirus that is endemic throughout much of North America.2,3 Infection with Jamestown Canyon virus may be asymptomatic or may result in a general febrile illness, meningitis, and/or meningoencephalitis.2,3 Beyond the above case report by Muqit, et al.,1 and another review article referencing this case report,4 Jamestown Canyon virus has not been reported to cause retinitis or other ocular manifestations.
Upon close review of the case report by Muqit, et al.,1 we believe the authors are likely describing a case of John Cunningham (JC) virus (a ubiquitous, double-stranded, deoxyribonucleic acid [DNA] human polyomavirus known to cause progressive multifocal leukoencephalopathy [PML] among the immunocompromised)5-7 rather than Jamestown Canyon virus.
First, the case patient with viral retinitis had underlying human immunodeficiency virus (HIV) infection and a low CD4 lymphocyte count (240 cells/mm3), making him immunocompromised and susceptible to reactivation of the John Cunningham (JC) virus. Second, the case patient had magnetic resonance imaging (MRI) brain findings (i.e., asymmetric, predominantly posterior, confluent, subcortical white matter hyperintensities involving U-fibers) that are classic for John Cunningham (JC) virus-related PML.6,7 In fact,...
Show MoreWe read with great interest the article by Forte et al1, "Swept source optical Coherence tomography Angiography in patients treated with hydroxychloroquine: co-relation of the functional and morphological test." Hydroxychloroquine (HCQ) is a widely used drug for the management of systemic lupus erythematosus and rheumatoid arthritis. Non-invasive tests like optical coherence tomography, optical coherence tomography-angiography, 10-2 visual fields and multifocal ERG (mf-ERG) help in the early detection of the toxicity.2 We would like to highlight here importance of adaptive optics, and various studies done for the early detection of HCQ toxicity. In the study by Forte et al, mf-ERG did not co-relate with the flow changes on OCT-A, however in another observation by Penrose et al (n=6) a depression of signals on multifocal ERG was found in the perifoveal region even when the patients had normal visual acuity and a normal fundus.3Costa et al found significant differences between the micro-perimetry in the patients taking hydroxychloroquine and controls.4 It will be interesting to know the authors take on this. Besides these, adaptive optics is emerging as an important tool to detect the early photo-receptor changes in patients with HCQ toxicity. Adaptive optics help in the direct visualization of the cone mosaic. Stepien et al in their observation on 4 patients observed that adaptive optics showed a loss of cone mosaic in the perifoveal region that corresponded with...
Show MoreShang et al. conducted a prospective study to examine the effect of ophthalmic and systemic conditions on incident dementia (1). The adjusted hazard ratios (HRs) (95% confidence intervals [CIs]) of age-related macular degeneration (AMD), cataract, diabetes-related eye disease (DRED), and glaucoma at baseline for incident dementia were 1.26 (1.05 to 1.52), 1.11 (1.00 to 1.24), 1.61 (1.30 to 2.00), and 1.07 (0.92 to 1.25), respectively. Diabetes, heart disease, stroke and depression at baseline were also significantly associated with an increased risk of dementia. In addition, some combinations of ophthalmic and systemic conditions were at the higher risk for incident dementia. I have a comment about the study.
Vision impairment is a risk factor of dementia, and poor vision is independently associated with a decline in cognitive function (2). Shang et al. clarified that AMD, cataract, and DRED were risk of incident dementia, and some combinations with systemic conditions accelerated risk of incident dementia. Although glaucoma was not significantly associated with increased risk of al-cause dementia, it was significantly associated with increased risk of vascular dementia. The authors also conducted analysis by excluding data in the first 5 years of follow-up, consistent results were also specified on the combined effects of ophthalmic and systemic conditions on incident dementia. Although the mechanism of increased risk of dementia in combinations with ophthalmic and...
Show MoreTo the editor,
We read with interest the recent publication by Bertolin et al. (“In vitro establishment, validation and characterisation of conjunctival epithelium outgrowth using tissue fragments and amniotic membrane”). Their validated conjunctival analogue of the simple limbal epithelial transplantation does represent a promising advance in the field. It is, however, interesting to note that the established tissue application was mainly validated on its growth potential and not specifically on its ability to reinstate a healthy ocular mucosal surface.
Functional validation is of utmost importance, especially as the glued fragments are directly transplanted. This approach circumvents the need for expensive cell culture but also bypasses the stringent release criteria for cell therapies or tissue-engineered transplantation products. We would suggest that before this technique can be considered fully validated, it should be demonstrated that the obtained conjunctival cells contribute to the first line of mucosal defence, i.e. barrier formation. Several conjunctival barriers can be identified, such as intercellular junction complexes, glycocalyx and secreted mucins. Bertolin et al. demonstrated the presence of tight junctions (cfr. ZO-1 protein) and a glycocalyx (cfr. membrane-associated mucin-1), but failed to address the presence of goblet cells. As goblet cells are responsible for the secretion of mucin 5AC, which is the most abundant mucin in the mucin la...
Show MoreWe like to congratulate Mullany et al. for their paper on normal-tension glaucoma is associated with cognitive impairment.1 To link normal-tension glaucoma (NTG) to cognitive impairment and therefore to a neurodegenerative process opens a new vista and research approach for glaucoma research. NTG indeed is an intriguing optic neuropathy that presents with a glaucomatous optic disc appearance and visual field loss similar to that seen in primary open angle glaucoma. The main risk factor for glaucoma however, increased intraocular pressure is missing.
Unlike other cranial nerves the optic nerve is a white matter tract of the brain, enveloped in the meninges (dura, arachnoid and pia mater) and surrounded by cerebrospinal fluid (CSF) on its entire length. And CSF indeed may be the link that connects the neurodegenerative process leading to cognitive impairment and the glaucomatous optic neuropathy in NTG. Recent research demonstrated a relationship between decreased CSF flow, measured in the ventricles and the spinal cord, and cognitive deficit in the elderly.2 In NTG, impaired CSF dynamics was demonstrated with computer assisted cisternography in the subarachnoid space of the intraorbital optic nerve most pronounced in the bulbar region behind the eye globe.3 In a recent publication we found an elevated L-PGDS concentration in the subarachnoid space of the optic nerve in NTG patients with optic nerve sheath compartment syndrome that results in a reduced CSF turnover.4...
Show MoreWe would like to congratulate Uwaydat et al. on their large series of spontaneously closed macular holes (MH), which adds new information to the literature.(1) It reinforces the observation that traumatic MH can spontaneously close and that a period of observation in these eyes, where the results of surgery are not clear, is a worthwhile option. However, we disagree with their conclusion that eyes with recent onset small primary MHs should also be observed. The authors don’t suggest a time period for observation but found that the median time for closure for these small holes was 4.4 months.
The report by Uwaydat et al. has 40 authors and the 60 cases of idiopathic MH were collected over at least a two-year period. Assuming a conservative number of 25 MH cases seen per surgeon per annum, this would give a spontaneous closure rate of ~3%, which is similar to the published literature as the authors review in their article.
MH are known to enlarge with time, even in the short term. Madi et al, reported that 83% enlarged, by a median of 105 microns in 8 weeks. (2) Similarly, Berton et al recently estimated that holes less than 250 microns enlarge by a mean of 1.67 microns per day, resulting in a similar 100-micron increase in 2 months.(3)
The anatomical and visual outcomes of surgery are dependent on MH diameter and duration. Holes greater than 300 microns, and with a duration more than four months are less likely to regain 0.3 logMAR or better.(4)...
Show MoreAtik et al (BJOhttps://bjo.bmj.com/content/105/5/602) have done an excellent job of summarizing the current state of the art for conducting health economic evaluations in ophthalmology. Not surprisingly, however, such tools and techniques were originally designed to address broader questions of healthcare funding and resource allocation across many disparate clinical areas. As such, the general use case was very far removed from ophthalmology. This is relevant as a central component is the calculation of the utility parameters used, particularly in cost-effectiveness calculations (1). At present, the standard default utility measure remains the EQ5D, which does not prima facie include a vision specific domain (2). Rather, a “Vision Bolt-On” to the EQ5D which asks patients whether they “Have no problems seeing”; “Have some problem seeing”; or “Have extreme problems seeing” is proposed for increasing the precision of the utility score derived from patients for ophthalmic interventions (3). Unfortunately, the “Vision Bolt On” while theoretically increasing the discriminating power of the EQ-5D has not been widely adopted in economic evaluations conducted in ophthalmology (3-4). Moreover, as currently configured, the “Vision Bolt On” questions fail to adequately account for the clinical differences, say between central or fine reading vision which may be more relevant in patients with age-related macular degeneration, versus...
Show MoreMartel et al. report the prevalence, features and risk factors of visual hallucinations following eye removal (1). The findings indicate that visual hallucinations may be a significant and prevalent association of eye amputation, occurring in around one-third of cases. Throughout the paper, visual hallucinations are referred to as phantom visions, and categorised under the broad catchment of the phantom eye syndrome that includes pain and tactile sensations as well as visual hallucinations. Although the authors speculate phantom visions could be considered a subtype of Charles Bonnet syndrome (CBS) they are reluctant to refer to them as CBS, perhaps because of the longstanding debate as to whether CBS should be used to refer to a specific type of visual hallucination or a specific underlying cause (2,3). Where CBS is used to refer to a specific hallucination type, it is typically reserved for complex hallucinations and excludes the simple, ‘elementary’ hallucinations described as the most common experiences following enucleation. The consequence is that a range of terms have evolved to describe symptoms that have the same cause, adding confusion to the literature and hindering research and extensive efforts to raise awareness and establish appropriate patient management pathways for people with visual hallucinations (4-6).
It is our opinion that both the simple and complex visual hallucinations described in the study should be referred to as Charles Bonnet syndrome....
Show MorePages