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We thank the authors[1] but wish to clarify several points. Stating that ‘glaucoma diagnosis is more common in OSA populations’ is controversial. Glaucoma diagnosis was not more common in our study (RR 1.01, CI 0.85-1.19), which censored prospectively from time of OSA coding throughout England from 1999-2011[2]. This is the largest and longest individual study conducted in this area. Several previous studies also observed no association.
The authors recommend accounting for ‘risk-associated conditions’. Accounting for potential confounders is important in evaluation of positive associations but less relevant in their absence. We agree that studies in different populations would be useful, particularly in Asia where OAG may differ.
In recommending a prospective RCT assessing ‘IOP/visual field progression before and after CPAP’, the authors are asking a different question. We have previously advocated this: ‘even in the absence of a positive association, it might still be relevant to identify those patients with genuine co-existence of OSA and POAG, particularly if evidence were to emerge … that OSA treatment could reduce glaucomatous progression’[2].
Our study never aimed to measure OSA point prevalence, so it is inappropriate to compare a speculative ‘base rate of 2.5%’ with prevalence estimates from a different continent/age-group. Moreover, our OSA cohort represented more severe disease; this should have exaggerated rather than ‘blurred’ any potentia...
We thank the authors[1] but wish to clarify several points. Stating that ‘glaucoma diagnosis is more common in OSA populations’ is controversial. Glaucoma diagnosis was not more common in our study (RR 1.01, CI 0.85-1.19), which censored prospectively from time of OSA coding throughout England from 1999-2011[2]. This is the largest and longest individual study conducted in this area. Several previous studies also observed no association.
The authors recommend accounting for ‘risk-associated conditions’. Accounting for potential confounders is important in evaluation of positive associations but less relevant in their absence. We agree that studies in different populations would be useful, particularly in Asia where OAG may differ.
In recommending a prospective RCT assessing ‘IOP/visual field progression before and after CPAP’, the authors are asking a different question. We have previously advocated this: ‘even in the absence of a positive association, it might still be relevant to identify those patients with genuine co-existence of OSA and POAG, particularly if evidence were to emerge … that OSA treatment could reduce glaucomatous progression’[2].
Our study never aimed to measure OSA point prevalence, so it is inappropriate to compare a speculative ‘base rate of 2.5%’ with prevalence estimates from a different continent/age-group. Moreover, our OSA cohort represented more severe disease; this should have exaggerated rather than ‘blurred’ any potential association.
The finding of a temporary elevation in OSA rate ratios soon after POAG diagnosis (offset later) is likely explained by increased effort screening for OSA through publicity around this potential association. These findings do not necessarily demonstrate a ‘lack of OSA screening’. Our findings do suggest that OSA screening might be directed towards AMD patients[3,4].
The recommendation of a ‘national OSA screening programme for all’ is a separate matter that should be judged on its own merits in an evidence-based manner.
References
1. Weir RE and Hozer KW. Ophthalmologists wake obstructive sleeping dogma. BJO 2017 eLetter
2. Keenan TD, Goldacre R, Goldacre MJ. Associations between obstructive sleep apnoea, primary open angle glaucoma and age-related macular degeneration: record linkage study. BJO 2017;101(2):155-159.
3. Keenan TD. Correspondence. Retina 2016;36(7):e70-1
4. Schaal S, Sherman MP, Nesmith B, Barak Y. Untreated obstructive sleep apnea hinders response to bevacizumab in age-related macular degeneration. Retina 2016;36(4):791-7
We read with interest the recently published study by Kim et al, which the authors described as a cross-sectional, observational, case-control study. As a single study such a design is not possible since cross-sectional and case-control studies are two distinct types of study designs. The authors compared the percent with lower lid epiblepharon between those with and without congenital glaucoma and reported that controls were matched on age and date of outpatient visit to the cases, which would suggest this is a matched case-control study. However, the statistical analysis employed did not account for the matched nature of the study design and therefore was not appropriate. Statistical procedures that account for the matched nature of the study should have been employed. The authors are urged to conduct a reanalysis of their study, amending their interpretation as warranted.
We read with great interest the article by Keenan et al. “Associations between obstructive sleep apnoea, primary open angle glaucoma and age-related macular degeneration: record linkage study” (Br J Ophthalmol. 2017 Feb;101(2):155-159), which concluded that Obstructive Sleep Apnoea (OSA) is not associated with Primary Open Angle Glaucoma (POAG). Potential POAG aetiology inflammatory markers are higher in OSA patients, and glaucoma diagnosis is more common in OSA populations.
While retrospective studies have great value, it is important to account for risk-associated conditions, including family history of OSA, racial disparities [1], smoking, hypertension, floppy eyelids, Type II diabetes [2], COPD and obesity.
To determine a causal relationship between OSA and POAG, it is necessary to assess intraocular pressures/visual field progression before and after continuous positive airway pressure (CPAP) treatment, using prospective randomised control trial designs. Further, the OSA base rate in Keenan et al. was 2.5%, while the estimated OSA prevalence rate may exceed 20% for those over 55 years of age [3]. Missing 90+% of apnoea sufferers may have blurred the true apnoea-POAG relationship. The risk rate for apnoea in the first year after initial POAG episode was 1.5, but declined to less than 1.0 in subsequent years, which suggests the possibility of increasing neglect of apnoea risk over the course of POAG. These findings highlight the lack of OSA screening and...
We read with great interest the article by Keenan et al. “Associations between obstructive sleep apnoea, primary open angle glaucoma and age-related macular degeneration: record linkage study” (Br J Ophthalmol. 2017 Feb;101(2):155-159), which concluded that Obstructive Sleep Apnoea (OSA) is not associated with Primary Open Angle Glaucoma (POAG). Potential POAG aetiology inflammatory markers are higher in OSA patients, and glaucoma diagnosis is more common in OSA populations.
While retrospective studies have great value, it is important to account for risk-associated conditions, including family history of OSA, racial disparities [1], smoking, hypertension, floppy eyelids, Type II diabetes [2], COPD and obesity.
To determine a causal relationship between OSA and POAG, it is necessary to assess intraocular pressures/visual field progression before and after continuous positive airway pressure (CPAP) treatment, using prospective randomised control trial designs. Further, the OSA base rate in Keenan et al. was 2.5%, while the estimated OSA prevalence rate may exceed 20% for those over 55 years of age [3]. Missing 90+% of apnoea sufferers may have blurred the true apnoea-POAG relationship. The risk rate for apnoea in the first year after initial POAG episode was 1.5, but declined to less than 1.0 in subsequent years, which suggests the possibility of increasing neglect of apnoea risk over the course of POAG. These findings highlight the lack of OSA screening and documentation, particularly in POAG sufferers, which should be confirmed with hypoxia measures that might better correlate with OSA pathology than other OSA diagnostic indices [4]. OSA risk screening tools (Berlin, STOPBANG sleep apnoea questionnaires) are readily available, are fast and simple to administer and score, and show acceptable rates of concordance with sleep study evidence of OSA [5]. We thank Keenan et al. for their important work and recommend a National OSA Screening program for all, including POAG patients.
References
1. O'Connor GT, Lind BK, Lee ET, Nieto FJ, Redline S, Samet JM, Boland LL, Walsleben JA, Foster GL; Sleep Heart Health Study Investigators.. Variation in symptoms of sleep-disordered breathing with race and ethnicity: the Sleep Heart Health Study. Sleep. 2003 Feb 1;26(1):74-9.
2. S.D. West, D.J. Nicoll, J.R. Stradling, Prevalence of obstructive sleep apnoea in men with type 2 diabetes, Thorax 61 (2006) 945–950.
3. Young T, Palta M, Dempsey J, Skatrud J, Weber S, Badr S. The occurrence of sleep-disordered breathing among middle-aged adults. N Engl J Med. 1993 Apr 29;328(17):1230-5.
4. Bianchi MT, Russo K, Gabbidon H, Smith T, Goparaju B, Westover MB. Big data in sleep medicine: prospects and pitfalls in phenotyping. Nat Sci Sleep. 2017 Feb 16;9:11-29.
5. Nagappa M, Liao P, Wong J, Auckley D, Ramachandran SK, Memtsoudis S, Mokhlesi B, Chung F. Validation of the STOP-Bang Questionnaire as a Screening Tool for Obstructive Sleep Apnea among Different Populations: A Systematic Review and Meta-Analysis. PLoS One. 2015 Dec 14;10(12):e0143697.
Short-term efficacy of intravitreal aflibercept depending on angiographic classification of polypoidal choroidal vasculopathy
Dan Calugaru, Mihai Calugaru
Department of Ophthalmology, Univ of Medicine Cluj-Napoca/Romania
Re: Short-term efficacy of intravitreal aflibercept depending on angiographic classification of polypoidal choroidal vasculopathy. Jeong and Sagong. Br J Ophthalmol 2016; http: /dx.doi. org/ 10.1136/bjophthalmol-2016-309144.
Dear Editor
We would like to address several challenges that have arisen from the study by Jeong and Sagong (1), which can be specifically summarized below.
1. The study included a relatively small sample size of cases examined with a fairly short follow-up period.
2. Several relevant data are missing in the study. For example, the anatomic types of macular edema (diffuse/cystic changes within neurosensory retina/subretinal/sub retinal pigment epithelium (RPE) fluid/ mixed type) at baseline and at months 3 and 6; the qualitative status of the 4 outer retinal layers (eg, the external limiting membrane band, the ellipsoid zone, the interdigitation zone, and the retinal pigment epithelial band) at presentation as well as the magnitude of changes (disruption/absence) during the study as potential predictors of visual loss/improvement after aflibercept (Eylea; Regeneron Pharmaceuticals Inc., Tarrytown, New York, USA) treatment; the percentages of patients with complete polyp regression and...
Short-term efficacy of intravitreal aflibercept depending on angiographic classification of polypoidal choroidal vasculopathy
Dan Calugaru, Mihai Calugaru
Department of Ophthalmology, Univ of Medicine Cluj-Napoca/Romania
Re: Short-term efficacy of intravitreal aflibercept depending on angiographic classification of polypoidal choroidal vasculopathy. Jeong and Sagong. Br J Ophthalmol 2016; http: /dx.doi. org/ 10.1136/bjophthalmol-2016-309144.
Dear Editor
We would like to address several challenges that have arisen from the study by Jeong and Sagong (1), which can be specifically summarized below.
1. The study included a relatively small sample size of cases examined with a fairly short follow-up period.
2. Several relevant data are missing in the study. For example, the anatomic types of macular edema (diffuse/cystic changes within neurosensory retina/subretinal/sub retinal pigment epithelium (RPE) fluid/ mixed type) at baseline and at months 3 and 6; the qualitative status of the 4 outer retinal layers (eg, the external limiting membrane band, the ellipsoid zone, the interdigitation zone, and the retinal pigment epithelial band) at presentation as well as the magnitude of changes (disruption/absence) during the study as potential predictors of visual loss/improvement after aflibercept (Eylea; Regeneron Pharmaceuticals Inc., Tarrytown, New York, USA) treatment; the percentages of patients with complete polyp regression and complete dry macula at month 6; the changes of central macular thickness (CMT) and subfoveal choroidal thickness (CT) at month 6; and the explanation of the mechanism by which the subfoveal CT was reduced after aflibercept therapy.
3. At baseline, the two groups of polypoidal choroidal vasculopathy (PCV) (2) were not comparable because there have been significant differences regarding the polyp number, branch vascular network (BVN) leakage, and subfoveal CT. The comparison should have been conducted only after using the multivariate regression analyses for adjustment of the baseline differences.
4. The comparative analysis of the 3-month outcomes highlighted a significant difference between the two groups relating to the reductions in the subfoveal CT, which was significantly higher in the type 2 PCV and no differences with respect to the percentages of the dry macula as well as the changes in the best corrected visual acuity (BCVA) score and CMT. The significantly higher proportion of the patients with complete polyp regression in the type 1 PCV should be interpreted considering the polyp number existing at baseline which was significantly higher in the type 1 than in the type 2 patients.
5. At 6 months, there was no significant difference in changes between the two groups regarding the percentages of the dry macula, BCVA score, and CMT. However, the evaluation of the treatment efficacy of aflibercept revealed a significant decrease of the subfoveal CT relative to the baseline values in the two types of PCV with a significantly greater reduction in the type 2 idiopathic PCV than the type 1 polypoidal choroidal neovascularisation. Conceivably, suppression of the choroidal vascular hyperpermeability and the vasoconstriction induced by aflibercept (3) may be more prominent in the type 2 PCV patients having a thicker choroid with abnormally enlarged and permeable choroidal vessels.
Altogether, in the short-term, the significant subfoveal CT thinning by aflibercept does not seem to result in visual deleterious changes. However, in the long-term, the prolonged inhibition of the vascular endothelial growth factor (VEGF) using aflibercept may affect the integrity of the choriocapillaris (CC) taking into account the key role played by the VEGF-A in the regulation of the survival and permeability of the CC. In addition, through the fragment cristalizable (Fc) domain, aflibercept can bind to the Fc receptor of both CC endothelial cells and red blood cells, leading to complement mediated cell death (4). Thus, the choroidal vascular impairment may affect the integrity of RPE and the outer retina with subsequent visual damaging effects because the choroid is involved in maintaining perfusion of the outer retinal layers and is the sole source of metabolic exchange for the fovea.
References
1. Jeong S, Sagong M. Short-term efficacy of intravitreal aflibercept depending on angiographic classification of polypoidal choroidal vasculopathy. Br J Ophthalmol 2016; http:/ dx. doi. org/ 10.1136/bjophthalmol-2016-309144.
2. Calugaru D. Calugaru M. Comparison of time to retreatment and visual function between ranibizumab and aflibercept in age-related macular degeneration. Am J Ophthalmol 2017;174:181-182.
3. Hata M, Oishi A, Tsujikawa A, et al. Efficacy of intravitreal injection of aflibercept in neovascular age-related macular degeneration with or without vascular hyperpermeability. Invest Ophthalmol Vis Sci 2014;55:7874-7880.
4. Julien S, Biesemeier A, Taubitz T, Schraermeyer U. Different effects of intravitreally injected ranibizumab and aflibercept on retinal and choroidal tissues of monkey eyes. Br J Ophthalmol 2014;98:Z813-825.
We have read with great interest Yokouchi et al’s article on the correlation between vascular endothelial growth factor (VEGF) levels and peripapillary retinal thickness in patients with POEMS syndrome(1) and we would like to share some reflections onthis mysterious form of optic neuropathy.
The acronym that gives name to the disorder does not include any ocular manifestation. However these patients frequently do develop ocular manifestations. Bilateral optic disc involvement appears in half of the patients and it has been considered an independent prognostic factor.(2)POEMS syndrome associated optic disc swelling constitutes a form of optic neuropathy that is not easy to classify. It is usually bilateral, but intracranial pressure is not elevated in most patients, so the term papilledema (although commonly used) is probably inaccurate. Most authors believe this optic neuropathy is related to increased VEGF levels, and Yokouchi et al’s work seems to support this theory.(1) From a pathogenic point of view optic disc swelling induced by cytokines should probably be considered a form of optic neuritis. However, inflammatory neuropathies often associate pain with eye movements and usually produce visual loss (reduced visual acuity and visual field damage) while POEMS patients present only minor visual disturbance and the visual prognosis is good.(3)
We suggest that POEMS associated optic disc swelling should be considered a new form of optic neuropathy. This neuro...
We have read with great interest Yokouchi et al’s article on the correlation between vascular endothelial growth factor (VEGF) levels and peripapillary retinal thickness in patients with POEMS syndrome(1) and we would like to share some reflections onthis mysterious form of optic neuropathy.
The acronym that gives name to the disorder does not include any ocular manifestation. However these patients frequently do develop ocular manifestations. Bilateral optic disc involvement appears in half of the patients and it has been considered an independent prognostic factor.(2)POEMS syndrome associated optic disc swelling constitutes a form of optic neuropathy that is not easy to classify. It is usually bilateral, but intracranial pressure is not elevated in most patients, so the term papilledema (although commonly used) is probably inaccurate. Most authors believe this optic neuropathy is related to increased VEGF levels, and Yokouchi et al’s work seems to support this theory.(1) From a pathogenic point of view optic disc swelling induced by cytokines should probably be considered a form of optic neuritis. However, inflammatory neuropathies often associate pain with eye movements and usually produce visual loss (reduced visual acuity and visual field damage) while POEMS patients present only minor visual disturbance and the visual prognosis is good.(3)
We suggest that POEMS associated optic disc swelling should be considered a new form of optic neuropathy. This neuropathy is probably due to the toxicity of elevated systemic VEGF and represents another manifestation of the organomegalia which characterizes the disease. We propose “VEGF-induced papillomegalia” as a more accurate term to designate optic nerve involvement in POEMS syndrome.
Reference List
1. Yokouchi H, Baba T, Misawa S, Sawai S, Kitahashi M, Oshitari T, et al. Correlation between peripapillary retinal thickness and serum level of vascular endothelial growth factor in patients with POEMS syndrome. Br J Ophthalmol. 2015.
2. Cui R, Yu S, Huang X, Zhang J, Tian C, Pu C. Papilloedema is an independent prognostic factor for POEMS syndrome. J Neurol. 2014;261(1):60-5.
3. Gonzalez-Martin-Moro J, Contreras I, Pilo-de-la-Fuente B, Gomez-Sanz F. Temporal and Spatial Correlation Between Choroidal Thickness and Visual Function in a Case of POEMS Syndrome. Ocul Immunol Inflamm. 2016:1-4.
We noticed the article entitled "Preoperative aqueous humour flare values do not predict proliferative vitreoretinopathy in patients with rhegmatogenous retinal detachment" by Mulder and associates with interest.(1)
Several studies have been published concluding that elevated aqueous flare values seem to be associated with increased risk for PVR redetachment.(2-4) Schroeder et al reported that values >15 photon counts per milliseconds (pc/ms) increases the risk for PVR 16-fold.(4) Hoerster et al showed that the odds ratio for PVR development with preoperative flare values >15pc/ms was 30.7 (p=0.0001) with a sensitivity of 80% and specificity of 79%.(3) Conart et al verified these findings (OR 12.3, p<0.0001 for later PVR in flare values >15 pc/ms).(2)
In contrast Mulder et al concluded on their data compilation that laser flare measurements are inaccurate in predicting PVR.(1) Logistic regression analyses showed a significant increase in odds with increasing flare at least for the second centre (1) supporting the notion that high flare measurements herald PVR. However, the large variation precluded sufficient sensitivity and specificity to separate between groups. We assume the reason for the large variation is that high-level outliers were included. For center 2 only the highest and the lowest values were excluded, no information is provided for center 1. Values of 100pc/ms, here up to 312pc/ms, are uncommon for the low-level type of i...
We noticed the article entitled "Preoperative aqueous humour flare values do not predict proliferative vitreoretinopathy in patients with rhegmatogenous retinal detachment" by Mulder and associates with interest.(1)
Several studies have been published concluding that elevated aqueous flare values seem to be associated with increased risk for PVR redetachment.(2-4) Schroeder et al reported that values >15 photon counts per milliseconds (pc/ms) increases the risk for PVR 16-fold.(4) Hoerster et al showed that the odds ratio for PVR development with preoperative flare values >15pc/ms was 30.7 (p=0.0001) with a sensitivity of 80% and specificity of 79%.(3) Conart et al verified these findings (OR 12.3, p<0.0001 for later PVR in flare values >15 pc/ms).(2)
In contrast Mulder et al concluded on their data compilation that laser flare measurements are inaccurate in predicting PVR.(1) Logistic regression analyses showed a significant increase in odds with increasing flare at least for the second centre (1) supporting the notion that high flare measurements herald PVR. However, the large variation precluded sufficient sensitivity and specificity to separate between groups. We assume the reason for the large variation is that high-level outliers were included. For center 2 only the highest and the lowest values were excluded, no information is provided for center 1. Values of 100pc/ms, here up to 312pc/ms, are uncommon for the low-level type of inflammation in primary rhegmatogenous retinal detachment. Therefore, we challenge laser flare values beyond 100pc/ms. Measurements become easily disturbed by background lighting or cells leading to the necessity to exclude measurements falsified by artefacts.
It would be interesting to know details on the protocol the authors followed to exclude artefacts. Furthermore, we would appreciate an explanation for the unusual variation of the values and the discrepant data towards previous reports.(2,4)
Reference List
1. Mulder VC, Tode J, van Dijk EH, Purtskhvanidze K, Roider J, Van Meurs JC et al. Preoperative aqueous humour flare values do not predict proliferative vitreoretinopathy in patients with rhegmatogenous retinal detachment. Br.J.Ophthalmol 2017. doi: 10.1136/bjophthalmol-2016-309134.
2. Conart JB, Kurun S, Ameloot F, Trechot F, Leroy B, Berrod JP. Validity of aqueous flare measurement in predicting proliferative vitreoretinopathy in patients with rhegmatogenous retinal detachment. Acta Ophthalmol 2016.
3. Hoerster R, Hermann MM, Rosentreter A, Muether PS, Kirchhof B, Fauser S. Profibrotic cytokines in aqueous humour correlate with aqueous flare in patients with rhegmatogenous retinal detachment. Br.J.Ophthalmol 2013;97:450-3.
4. Schroder S, Muether PS, Caramoy A, Hahn M, Abdel-Salam M, Diestelhorst M et al. Anterior chamber aqueous flare is a strong predictor for proliferative vitreoretinopathy in patients with rhegmatogenous retinal detachment. Retina 2012;32:38-42.
Morphological and functional changes in recalcitrant diabetic
macular oedema after intravitreal dexamethasone implant.
Dan Calugaru, Mihai Calugaru
Department of Ophthalmology, Univ of Medicine Cluj-Napoca/Romania
Re: Morphological and functional changes in recalcitrant diabetic
macular oedema after intravitreal dexamethasone implant. Iacono et al. Br
J Ophthalmol 2016;http:/dx.doi.org/10.1136/bjophthalmol-201...
Morphological and functional changes in recalcitrant diabetic
macular oedema after intravitreal dexamethasone implant.
Dan Calugaru, Mihai Calugaru
Department of Ophthalmology, Univ of Medicine Cluj-Napoca/Romania
Re: Morphological and functional changes in recalcitrant diabetic
macular oedema after intravitreal dexamethasone implant. Iacono et al. Br
J Ophthalmol 2016;http:/dx.doi.org/10.1136/bjophthalmol-2016-308726.
Dear Editor
We would like to address several challenges that have arisen from the
study by Iacono et al (1), which can be specifically summarized below.
1. The study was uncontrolled and was carried out on a small study
population. There was a selection bias attributable to the heterogeneous
prior treatments administered to the patients, namely, panretinal
photocoagulation (PRP), grid photocoagulation, focal laser
photocoagulation, and anti-vascular endothelial growth factor (VEGF)
injections. Nothing was stated regarding the existence of a washout period
between previous PRP, focal/grid laser treatment and the first
dexamethasone implant.
2. Three outer retinal layers (eg, the external limiting membrane,
the ellipsoid zone, and retinal pigment epithelium [RPE]) were thoroughly
investigated as potential predictors of vision loss/improvement. There are
no data on the qualitative status of the fourth outer retinal layers, that
is, the interdigitation zone, which corresponds to the contact cylinder
represented by the apices of the RPE cells that encase part of the cone
outer segments.
3. Nothing was stated referring to the prevalence of the
vitreoretinal interface abnormalities (eg, vitreomacular adhesion/traction
and epiretinal membranes) and their changes during the study as potential
predictive factors on anatomical and visual outcomes after dexamethasone
implant in eyes affected by recalcitrant diabetic macular oedema (DME)
associated with proliferative diabetic retinopathy.
4. In the assessment of the final results of this study we have
considered the current assertion that evaluation of outcomes has to be
guided by anatomical measure data with visual changes as a secondary guide
(2). Accordingly, the outcomes of this series are unsatisfactory. Despite
a mean gain of approximately 10 Early Treatment Diabetic Retinopathy Study
letters in visual acuity correlated with a significant improvement in the
integrity of the outer retinal layers, the central macular thickness (CMT)
decreased significantly to 423 microns after treatment, a value that is
more than the cutoff for the upper level of normal CMT (3). Persistence of
this high value of the CMT highlights unresolved macular edema and
indicates that the disease process is still active and progressive,
requiring further treatment with antiangiogenic agents.
5. The patients in the present study suffered from persistent DME
with a 30.3 months'duration of the disease, who have been treated with an
average of 2.2 dexamethasone implants within the 12-month follow-up, a
number of injections which has proved to be insufficient to obtain dryness
of the macula. These facts favored the delayed occurrence of a chronic
retinal capillaropathy owing to permanent breakdown of the inner and outer
blood-retinal barriers (eg, pigmentary changes in the fovea, poorly
controlled severe recurrent macular edema, telangiectatic vessels with
leakage, and epiretinal membrane formation). This permanent retinal
capillaropathy was temporarily relieved by reduction of oedematous
component with treatment. However, this condition is incurable owing to
the irreversible ischemic lesions to the macular ganglion cell complex,
close to the foveola, with macular oedema being a minor factor.
Altogether, regardless of the therapeutic agents chosen (anti-VEGF
agents/corticosteroids), the efficacy of therapy depends primarily on the
promptness of the treatment after DME diagnosis. Any delay in treatment
will adversely influence the restoration of visual functions, which are
difficult to correct even with subsequent treatment (4,5).
References
1. Iacono P, Parodi MB, Scaramuzzi M, et al. Morphological and functional
changes in recalcitrant diabetic macular oedema after intravitral
dexamethasone implant. Br J Ophthalmol 2016;
http:/dx.doi.org/10.1136/bjophthalmol-2016-308726.
2. Freund KB, Korobelnik JF, Devenyl R, et al. Treat-and-extend regimens
with anti-VEGF agents in retinal diseases. Aliterature review and
consensus recommendations. Retina 2015;35(8):1489-1506.
3. Gover S, Murthy RK, Brar VS, et al. Normative data for macular
thickness by high-definition spectral-domain optical coherence tomography
(spectralis). Am J Ophthalmol 2009;148(2):266-271.
4. Calugaru D. Calugaru M. Real-world outcomes of ranibizumab treatment
for diabetic macular edema in a United Kingdom National Health Service
setting. Am J Ophthalmol 2017;174:175-176.
5. Calugaru D, Calugaru M. Comments to: Long-term efficacy and safety of
intrvitreal dexamethasone implant for the treatment of diabetic macular
edema. Eur J Ophthalmol 2016;26(6):e171-e172.
Response to: Role of Case Series Studies in the Identification of Anaesthetic Complications
Dear Editor,
We would like to acknowledge Eke and Kumar for their comments on our article.1
In our retrospective case series study of 12,992 patients, we noted that subtenon anaesthesia had more complications and that both topical and subtenon anaesthesia in our series were the ideal anaesthetics.
Response to: Role of Case Series Studies in the Identification of Anaesthetic Complications
Dear Editor,
We would like to acknowledge Eke and Kumar for their comments on our article.1
In our retrospective case series study of 12,992 patients, we noted that subtenon anaesthesia had more complications and that both topical and subtenon anaesthesia in our series were the ideal anaesthetics.
Retrospective case series studies still play an important role in the progress of medical science2 with aims that complement other research designs in the pursuit of evidence.3 Shyam et al further noted that case series studies are well placed at the apex of hypothesis generation and play a role in the identification of side effects and complications4 as similarly intended in our study. Further, other case series studies5,6 and a systematic review of case series7 have sought to analyze the association of side effects and complications with surgical treatment and procedures.
Almost all cases of phacoemulsification were conducted under topical anaesthesia in our set-up. This included cases where difficulties were anticipated such as pseudoexfoliation, small pupils and dense cataracts. The switch to topical was made in recent years once the surgeons were comfortable and convinced that topical anaesthesia works well without complications of injections and patients were happy with the white eye appearance. A recent Cochrane review on the topic noted that "all trials were performed at a time when surgeons were only starting to use topical anesthesia".8 In light of this, we look forward to further research as surgeons become more proficient in their use of topical anesthesia.
References
1. Thevi T, Godinho MA. Trends and complications of local anaesthesia in cataract surgery: an 8-year analysis of 12 992 patients. Br J Ophthalmol 2016;100:1708-1713.
2. Vandenbroucke JP. Case reports in an evidence-based world. J R Soc Med. 1999;92:159-63.
3. Vandenbroucke JP. In defense of case reports and case series. Ann Intern Med 2001;134(4):330-4.
4. Shyam A, Shetty G. Case Reports and Evidence Based Medicine: Redefining the Apex of the Triangle. J Orthop Case Rep 2012;2(2):1-2.
5. Saito Y1, Uraoka T, Matsuda T, Emura F, Ikehara H, Mashimo Y, Kikuchi T, Fu KI, Sano Y, Saito D. Endoscopic treatment of large superficial colorectal tumors: a case series of 200 endoscopic submucosal dissections (with video). Gastrointest Endosc 2007;66(5):966-73.
6. Sowash M, Barzilai O, Kahn S, McLaughlin L, Boland P, Bilsky MH, Laufer I. Clinical outcomes following resection of giant spinal schwannomas: a case series of 32 patients. J Neurosurg Spine. 2017;13:1-7. doi: 10.3171/2016.9.SPINE16778.
7. Hasimoto CN, Cataneo C, Eldib R, Thomazi R, Pereira RS, Minossi JG, Cataneo AJ. Efficacy of surgical versus conservative treatment in esophageal perforation: a systematic review of case series studies. Acta Cir Bras 2013;28(4):266-71.
8. Guay J, Sales K. Sub-Tenon's anaesthesia versus topical anaesthesia for cataract surgery. Cochrane Database of Systematic Reviews 2015; Issue 8. Art. No.: CD006291. DOI: 10.1002/14651858.CD006291.pub3.
We read Thevi and Godhino's article (1) with interest, but we feel
that the methodology does not support their conclusions. They aimed to
'find out the most suitable anaesthesia for patients with fewer
complications' in cataract surgery, and reported that 'sub-Tenon
anaesthesia [STA] was associated with more intraoperative and
postoperative complications ... topical anaesthesia [TA] ... is the ideal
a...
We read Thevi and Godhino's article (1) with interest, but we feel
that the methodology does not support their conclusions. They aimed to
'find out the most suitable anaesthesia for patients with fewer
complications' in cataract surgery, and reported that 'sub-Tenon
anaesthesia [STA] was associated with more intraoperative and
postoperative complications ... topical anaesthesia [TA] ... is the ideal
anaesthesia'(1). However, this was a retrospective observational case-
series, not a randomised study. Therefore, any association does not
necessarily imply causation. We believe that the authors have overlooked
other more plausible explanations for an association between STA and
surgical complications.
The paper does not explain why some patients had STA and others TA.
Many surgeons use TA for uncomplicated phacoemulsification, and STA or
other blocks when surgical difficulties are anticipated: e.g. small pupil,
dense cataract. For very dense cataracts, large-incision (manual)
cataract surgery may be preferred: this has a different complication
profile, and generally requires STA or other blocks. We suspect that
surgeons chose STA for "higher-risk" cataracts, and this could easily
explain the higher complication rate.
There have been few randomised trials comparing surgical complication
rates for TA and STA. The recent Cochrane review concluded 'there was not
enough evidence to suggest that one technique would result in a higher or
lower incidence of intraoperative complications' and predicted that a
randomised trial comprising 116,884 eyes would be required.(2)
We agree that, for many cases, topical (or topical-intracameral)
anaesthesia may be the nearest to an 'ideal' anaesthesia, but for many
other cases, STA may be nearest to the ideal. Joint Colleges Guideline
2012 stated: "When deciding which type of anaesthesia to use,
consideration needs to be given to patient, surgical and operator
factors....No local anaesthetic technique is entirely safe."(3) Clinicians
should continue to use informed judgement in recommending appropriate
anaesthesia for their patients.
Tom Eke, Consultant Ophthalmologist, Norwich and Norfolk University
Hospital, Norwich, UK
Chandra M Kumar, Professor and Senior Consultant in Anaesthesia, Khoo
Teck Puat Hospital, Singapore
References
1. Thevi T, Godinho MA. Trends and complications of local
anaesthesia in cataract surgery: an 8-year analysis of 12 992 patients.
Br J Ophthalmol 2016;100:1708-1713.
2. Guay J, Sales K. Sub-Tenon's anaesthesia versus topical anaesthesia
for cataract surgery. Cochrane Database of Systematic Reviews 2015, Issue
8. Art. No.: CD006291. DOI: 10.1002/14651858.CD006291.pub3.
3. Kumar CM, Eke T, Dodds C, et al. Local Anaesthesia for Ophthalmic
Surgery. Royal College of Anaesthetists, Royal College of
Ophthalmologists, London; 2012.
We read with great interest article entitled "Five-year results of
Small Incision Lenticule Extraction (ReLEx SMILE)" by Blum et al (1). They
concluded SMILE to be an effective, stable and safe procedure for
treatment of myopia and myopic astigmatism in the long term. However, few
queries come to our mind.
In their study they observed regression of 0.48 D over a period of
five years, which they attributed mainly...
We read with great interest article entitled "Five-year results of
Small Incision Lenticule Extraction (ReLEx SMILE)" by Blum et al (1). They
concluded SMILE to be an effective, stable and safe procedure for
treatment of myopia and myopic astigmatism in the long term. However, few
queries come to our mind.
In their study they observed regression of 0.48 D over a period of
five years, which they attributed mainly to a subset of seven eyes.
Although, in one eye cap perforation was noted, other six eye's regression
was assumed to be result of long-term growth of the axial length, as most
of these patients were 24 - 25 years of age at time of surgery. As a
beginner, it would be helpful to us if a nomogram can be devised according
to age as most of our patient undergoing SMILE are in the age group of 22
to 30 years to obviate unexpected outcomes. Present study being the
longest follow up study till date, offers to be a perfect setting for such
an analytical observation, providing further refinement of our refractive
procedure. We encourage the authors to do the same.
Authors also mentioned corneal topography and higher order
aberrations(HOA) using Wave front measurements in methods section, but no
results regarding the same were described. As most of the studies suggest
that the posterior corneal surface remains stable till one year follow up
(2,3), it would have been interesting to note the long term changes in
posterior elevation. Similarly, most of the studies have reported SMILE to
induce HOA's, though less than LASIK but no long term results are there
(4,5). Such analysis would again strengthen the safety of profile offered
by SMILE.
We congratulate the authors on a thorough research and hope our
discussion adds to their work.
References:
1. Blum M, Taubig K, Gruhn C, Sekundo W, Kunert KS. Five-year results
of small incision lenticule extraction (ReLEx SMILE). Br J Ophthalmol.
2016 Sep;100(9):1192-5.
2. Zhao Y, Li M, Zhao J, Knorz MC, Sun L, Tian M, Zhou X. Posterior
corneal elevation after small incision lenticule extraction for moderate
and high myopia.PLoS One. 2016 Feb10;11(2):e0148370.
3. MM Wang B, Zhang Z, Naidu RK, Chu R, Dai J, Qu X, Yu Z, Zhou H.
Comparison of the change in posterior corneal elevation and corneal
biomechanical parameters after small incision lenticule extraction and
femtosecond laser-assisted LASIK for myopia correction. Cont Lens Anterior
Eye. 2016 Jun;39(3):191-6.
5. Wu W, Wang Y. Corneal higher-order aberrations of the anterior
surface,posterior surface, and total cornea after SMILE, FS-LASIK, and
FLEx surgeries. Eye Contact Lens. 2016 Nov;42(6):358-365.
We thank the authors[1] but wish to clarify several points. Stating that ‘glaucoma diagnosis is more common in OSA populations’ is controversial. Glaucoma diagnosis was not more common in our study (RR 1.01, CI 0.85-1.19), which censored prospectively from time of OSA coding throughout England from 1999-2011[2]. This is the largest and longest individual study conducted in this area. Several previous studies also observed no association.
The authors recommend accounting for ‘risk-associated conditions’. Accounting for potential confounders is important in evaluation of positive associations but less relevant in their absence. We agree that studies in different populations would be useful, particularly in Asia where OAG may differ.
In recommending a prospective RCT assessing ‘IOP/visual field progression before and after CPAP’, the authors are asking a different question. We have previously advocated this: ‘even in the absence of a positive association, it might still be relevant to identify those patients with genuine co-existence of OSA and POAG, particularly if evidence were to emerge … that OSA treatment could reduce glaucomatous progression’[2].
Our study never aimed to measure OSA point prevalence, so it is inappropriate to compare a speculative ‘base rate of 2.5%’ with prevalence estimates from a different continent/age-group. Moreover, our OSA cohort represented more severe disease; this should have exaggerated rather than ‘blurred’ any potentia...
Show MoreWe read with interest the recently published study by Kim et al, which the authors described as a cross-sectional, observational, case-control study. As a single study such a design is not possible since cross-sectional and case-control studies are two distinct types of study designs. The authors compared the percent with lower lid epiblepharon between those with and without congenital glaucoma and reported that controls were matched on age and date of outpatient visit to the cases, which would suggest this is a matched case-control study. However, the statistical analysis employed did not account for the matched nature of the study design and therefore was not appropriate. Statistical procedures that account for the matched nature of the study should have been employed. The authors are urged to conduct a reanalysis of their study, amending their interpretation as warranted.
We read with great interest the article by Keenan et al. “Associations between obstructive sleep apnoea, primary open angle glaucoma and age-related macular degeneration: record linkage study” (Br J Ophthalmol. 2017 Feb;101(2):155-159), which concluded that Obstructive Sleep Apnoea (OSA) is not associated with Primary Open Angle Glaucoma (POAG). Potential POAG aetiology inflammatory markers are higher in OSA patients, and glaucoma diagnosis is more common in OSA populations.
While retrospective studies have great value, it is important to account for risk-associated conditions, including family history of OSA, racial disparities [1], smoking, hypertension, floppy eyelids, Type II diabetes [2], COPD and obesity.
To determine a causal relationship between OSA and POAG, it is necessary to assess intraocular pressures/visual field progression before and after continuous positive airway pressure (CPAP) treatment, using prospective randomised control trial designs. Further, the OSA base rate in Keenan et al. was 2.5%, while the estimated OSA prevalence rate may exceed 20% for those over 55 years of age [3]. Missing 90+% of apnoea sufferers may have blurred the true apnoea-POAG relationship. The risk rate for apnoea in the first year after initial POAG episode was 1.5, but declined to less than 1.0 in subsequent years, which suggests the possibility of increasing neglect of apnoea risk over the course of POAG. These findings highlight the lack of OSA screening and...
Show MoreShort-term efficacy of intravitreal aflibercept depending on angiographic classification of polypoidal choroidal vasculopathy
Dan Calugaru, Mihai Calugaru
Department of Ophthalmology, Univ of Medicine Cluj-Napoca/Romania
Re: Short-term efficacy of intravitreal aflibercept depending on angiographic classification of polypoidal choroidal vasculopathy. Jeong and Sagong. Br J Ophthalmol 2016; http: /dx.doi. org/ 10.1136/bjophthalmol-2016-309144.
Dear Editor
Show MoreWe would like to address several challenges that have arisen from the study by Jeong and Sagong (1), which can be specifically summarized below.
1. The study included a relatively small sample size of cases examined with a fairly short follow-up period.
2. Several relevant data are missing in the study. For example, the anatomic types of macular edema (diffuse/cystic changes within neurosensory retina/subretinal/sub retinal pigment epithelium (RPE) fluid/ mixed type) at baseline and at months 3 and 6; the qualitative status of the 4 outer retinal layers (eg, the external limiting membrane band, the ellipsoid zone, the interdigitation zone, and the retinal pigment epithelial band) at presentation as well as the magnitude of changes (disruption/absence) during the study as potential predictors of visual loss/improvement after aflibercept (Eylea; Regeneron Pharmaceuticals Inc., Tarrytown, New York, USA) treatment; the percentages of patients with complete polyp regression and...
We have read with great interest Yokouchi et al’s article on the correlation between vascular endothelial growth factor (VEGF) levels and peripapillary retinal thickness in patients with POEMS syndrome(1) and we would like to share some reflections onthis mysterious form of optic neuropathy.
Show MoreThe acronym that gives name to the disorder does not include any ocular manifestation. However these patients frequently do develop ocular manifestations. Bilateral optic disc involvement appears in half of the patients and it has been considered an independent prognostic factor.(2)POEMS syndrome associated optic disc swelling constitutes a form of optic neuropathy that is not easy to classify. It is usually bilateral, but intracranial pressure is not elevated in most patients, so the term papilledema (although commonly used) is probably inaccurate. Most authors believe this optic neuropathy is related to increased VEGF levels, and Yokouchi et al’s work seems to support this theory.(1) From a pathogenic point of view optic disc swelling induced by cytokines should probably be considered a form of optic neuritis. However, inflammatory neuropathies often associate pain with eye movements and usually produce visual loss (reduced visual acuity and visual field damage) while POEMS patients present only minor visual disturbance and the visual prognosis is good.(3)
We suggest that POEMS associated optic disc swelling should be considered a new form of optic neuropathy. This neuro...
We noticed the article entitled "Preoperative aqueous humour flare values do not predict proliferative vitreoretinopathy in patients with rhegmatogenous retinal detachment" by Mulder and associates with interest.(1)
Several studies have been published concluding that elevated aqueous flare values seem to be associated with increased risk for PVR redetachment.(2-4) Schroeder et al reported that values >15 photon counts per milliseconds (pc/ms) increases the risk for PVR 16-fold.(4) Hoerster et al showed that the odds ratio for PVR development with preoperative flare values >15pc/ms was 30.7 (p=0.0001) with a sensitivity of 80% and specificity of 79%.(3) Conart et al verified these findings (OR 12.3, p<0.0001 for later PVR in flare values >15 pc/ms).(2)
In contrast Mulder et al concluded on their data compilation that laser flare measurements are inaccurate in predicting PVR.(1) Logistic regression analyses showed a significant increase in odds with increasing flare at least for the second centre (1) supporting the notion that high flare measurements herald PVR. However, the large variation precluded sufficient sensitivity and specificity to separate between groups. We assume the reason for the large variation is that high-level outliers were included. For center 2 only the highest and the lowest values were excluded, no information is provided for center 1. Values of 100pc/ms, here up to 312pc/ms, are uncommon for the low-level type of i...
Show MoreMorphological and functional changes in recalcitrant diabetic macular oedema after intravitreal dexamethasone implant. Dan Calugaru, Mihai Calugaru Department of Ophthalmology, Univ of Medicine Cluj-Napoca/Romania
Re: Morphological and functional changes in recalcitrant diabetic macular oedema after intravitreal dexamethasone implant. Iacono et al. Br J Ophthalmol 2016;http:/dx.doi.org/10.1136/bjophthalmol-201...
Retrospective case series studies s...
Editor,
We read Thevi and Godhino's article (1) with interest, but we feel that the methodology does not support their conclusions. They aimed to 'find out the most suitable anaesthesia for patients with fewer complications' in cataract surgery, and reported that 'sub-Tenon anaesthesia [STA] was associated with more intraoperative and postoperative complications ... topical anaesthesia [TA] ... is the ideal a...
We read with great interest article entitled "Five-year results of Small Incision Lenticule Extraction (ReLEx SMILE)" by Blum et al (1). They concluded SMILE to be an effective, stable and safe procedure for treatment of myopia and myopic astigmatism in the long term. However, few queries come to our mind.
In their study they observed regression of 0.48 D over a period of five years, which they attributed mainly...
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