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We read with great interest the study by Salowi and colleagues,[1] analysing risk factors for posterior capsular rupture (PCR) in over 150,000 cataract operations across Malaysia. Many of the significant risk factors were expected and well-recognised, such as junior surgeon or pseudoexfoliation. An interesting finding was increased PCR in males, with odd ratio 1.11 (95% confidence interval 1.04 to 1.17).
Male gender has been found to be a risk factor for PCR in other large retrospective studies. The Cataract National Dataset of 55,567 cataract operations across 12 National Health Service Trusts in the UK found male gender to have an adjusted odds ratio of 1.28 (95% CI 1.13-1.45).[2] We recently reviewed 62,994 cataract operations performed at Moorfields, showing male gender as a significant risk for PCR, with OR 1.490 (95% CI 1.274–1.741).[3] This risk was similar to junior surgeon (OR 1.483) or prior intravitreal injection (OR 1.664), an increasingly acknowledged predictor of complicated surgery.
The reasons for increased PCR in male patients is unclear. Males are significantly more likely to take tamsulosin, an alpha receptor blocker used in the treatment of benign prostatic hypertrophy. This can lead to poor pupillary dilation and intraoperative floppy iris syndrome (IFIS).[4] Although this can be effectively managed with intracameral phenylephrine, iris hooks or Malyugin ring, it remains a risk factor for PCR. Furthermore, males are more likely to be aff...
We read with great interest the study by Salowi and colleagues,[1] analysing risk factors for posterior capsular rupture (PCR) in over 150,000 cataract operations across Malaysia. Many of the significant risk factors were expected and well-recognised, such as junior surgeon or pseudoexfoliation. An interesting finding was increased PCR in males, with odd ratio 1.11 (95% confidence interval 1.04 to 1.17).
Male gender has been found to be a risk factor for PCR in other large retrospective studies. The Cataract National Dataset of 55,567 cataract operations across 12 National Health Service Trusts in the UK found male gender to have an adjusted odds ratio of 1.28 (95% CI 1.13-1.45).[2] We recently reviewed 62,994 cataract operations performed at Moorfields, showing male gender as a significant risk for PCR, with OR 1.490 (95% CI 1.274–1.741).[3] This risk was similar to junior surgeon (OR 1.483) or prior intravitreal injection (OR 1.664), an increasingly acknowledged predictor of complicated surgery.
The reasons for increased PCR in male patients is unclear. Males are significantly more likely to take tamsulosin, an alpha receptor blocker used in the treatment of benign prostatic hypertrophy. This can lead to poor pupillary dilation and intraoperative floppy iris syndrome (IFIS).[4] Although this can be effectively managed with intracameral phenylephrine, iris hooks or Malyugin ring, it remains a risk factor for PCR. Furthermore, males are more likely to be affected by trauma, and traumatic cataract carries an increased risk of PCR. We would welcome further discussion of this less recognised risk factor for PCR.
References:
1. Salowi MA, Chew FLM, Adnan TH, Ismail M, Goh PP: The Malaysian Cataract Surgery Registry: risk Indicators for posterior capsular rupture. The British journal of ophthalmology 2017.
2. Narendran N, Jaycock P, Johnston RL, Taylor H, Adams M, Tole DM, Asaria RH, Galloway P, Sparrow JM: The Cataract National Dataset electronic multicentre audit of 55,567 operations: risk stratification for posterior capsule rupture and vitreous loss. Eye (London, England) 2009, 23(1):31-37.
3. Shalchi Z, Okada M, Whiting C, Hamilton R: Risk of Posterior Capsule Rupture During Cataract Surgery in Eyes With Previous Intravitreal Injections. American journal of ophthalmology 2017, 177:77-80.
4. Chatziralli IP, Peponis V, Parikakis E, Maniatea A, Patsea E, Mitropoulos P: Risk factors for intraoperative floppy iris syndrome: a prospective study. Eye (London, England) 2016, 30(8):1039-1044.
I whole heartedly appreciate the work conducted by Chan Yun Kim et al in studying the treatment patterns and medication adherence of patients with glaucoma in South Korea.This study concluded that medication non adherence was seen more commonly in males , increased daily number of administration and increase in the number of eyedrops. We have also conducted a similar study at our centre in North India and would like to share our results .Our results are in agreement to the work conducted by Chan Yun Kim stating that increased number of instillation and increased number of eyedrops contribute significantly to medication non adherence. However, in our study we also found that medication adherence varies in different severity grades of glaucoma with severe stages being significantly more adherent than mild to moderate stages of glaucoma.Additionally, there was no difference found in medication adherence among males or females.
We again express our gratitude to the researcher in enlightening our minds regarding medication adherence in South Korean population.
We thank Sarmad et al. for their interest in our publication. Our study is a retrospective review of several variables regarding non-traumatic corneal perforations (1). In handling clinical records for a retrospective analysis, missing variables represent a common problem. In relation to the location of corneal perforation, information was not available in 25 eyes thus the number does not match. Hence, in consideration of this inevitable flaw we decided not to include the anatomical location of perforation into the model presented in the manuscript, therefore all the variables included in this statistical model had no missing values.
Clinical treatment of corneal perforation is often complex and a single intervention may not address the patient full pathology, therefore more than one treatment is frequently used. (2) This explains the increased number of initial treatments in the first clinical intervention, one example of this scenario are the patients needing simultaneous tectonic penetrating keratoplasty to restore ocular integrity and concurrent amniotic membrane transplantation to aid in the control of ocular surface. (2)(3)
These two situations might not be precise in our manuscript, but we take the opportunity of this letter to clarify them. However, that is unquestionably far from compromising the validity of the conclusions. Definitely, as any retrospective study, and as we mention in the discussion of our article, there are li...
We thank Sarmad et al. for their interest in our publication. Our study is a retrospective review of several variables regarding non-traumatic corneal perforations (1). In handling clinical records for a retrospective analysis, missing variables represent a common problem. In relation to the location of corneal perforation, information was not available in 25 eyes thus the number does not match. Hence, in consideration of this inevitable flaw we decided not to include the anatomical location of perforation into the model presented in the manuscript, therefore all the variables included in this statistical model had no missing values.
Clinical treatment of corneal perforation is often complex and a single intervention may not address the patient full pathology, therefore more than one treatment is frequently used. (2) This explains the increased number of initial treatments in the first clinical intervention, one example of this scenario are the patients needing simultaneous tectonic penetrating keratoplasty to restore ocular integrity and concurrent amniotic membrane transplantation to aid in the control of ocular surface. (2)(3)
These two situations might not be precise in our manuscript, but we take the opportunity of this letter to clarify them. However, that is unquestionably far from compromising the validity of the conclusions. Definitely, as any retrospective study, and as we mention in the discussion of our article, there are limitations including the lack of a standard algorithm of treatment and the impossibility to include other variables that might alter the final outcomes of the patients. Therefore, and as we also discussed, this imply that the conclusions presented must be taken with caution. Thus, when interpreting the results of a retrospective study it is important to understand and be aware of the possible bias and limitations, allowing the reader to take advantage of the many strengths of this design into incorporation of knowledge into their daily clinical practice. (4)
References.
1) Loya-Garcia D, Serna-Ojeda JC, Pedro-Aguilar L, et al. Non-traumatic corneal perforations: aetiology, treatment and outcomes. Br J Ophthalmol. 2017;101(5):634-639.
2) Jhanji V, Young AL, Mehta JS, et al. Management of corneal perforation. Surv Ophthalmol. 2011;56(6):522-38.
3) Dua HS, Gomes JA, King AJ, et al. The Amniotic Membrane in Ophthalmology. Surv Opthalmol 2004; 49:51-77.
4) Euser AM, Zoccali C, Jager KJ, et al. Cohort studies: prospective versus retrospective. Nephron Clin Pract. 2009;113(3):c214-7.
We warmly thank Calugaru D and associates for their correspondence regarding our article entitled " Early response to ranibizumab predictive of functional outcome after dexamethasone for unresponsive diabetic macular oedema".1
We agree with them about some of the challenges concerning our study. As we have acknowledged in the limitation section of our article, our study is limited by several biases, as its design was retrospective. In particular, patients selection and follow-up represented some of the major flaws in our study. We collected data about patients switched to dexamethasone for different reasons; some patients were treatment-naïve, other had already undergone treatments for diabetic macular edema (DME). No one disclosed any feature of chronic long-standing DME; all of them received prompt therapy after DME diagnosis.
Some of them showed a good response to ranibizumab loading-dose, with satisfying reduction of macular thickness after the injections. Nevertheless, no patient disclosed a completely dry macula after the anti-vascular endothelial growth factor (VEGF) loading-dose.
As far as it regards the final functional and anatomical gain at the end of the follow-up, the Authors state that the outcomes of this series were unsatisfactory. However, in the non-responders group, despite initial poor results, the best-corrected visual acuity (BCVA) had improved significantly (p<0.05) and clinically (> 5 letters), as highlighted in the...
We warmly thank Calugaru D and associates for their correspondence regarding our article entitled " Early response to ranibizumab predictive of functional outcome after dexamethasone for unresponsive diabetic macular oedema".1
We agree with them about some of the challenges concerning our study. As we have acknowledged in the limitation section of our article, our study is limited by several biases, as its design was retrospective. In particular, patients selection and follow-up represented some of the major flaws in our study. We collected data about patients switched to dexamethasone for different reasons; some patients were treatment-naïve, other had already undergone treatments for diabetic macular edema (DME). No one disclosed any feature of chronic long-standing DME; all of them received prompt therapy after DME diagnosis.
Some of them showed a good response to ranibizumab loading-dose, with satisfying reduction of macular thickness after the injections. Nevertheless, no patient disclosed a completely dry macula after the anti-vascular endothelial growth factor (VEGF) loading-dose.
As far as it regards the final functional and anatomical gain at the end of the follow-up, the Authors state that the outcomes of this series were unsatisfactory. However, in the non-responders group, despite initial poor results, the best-corrected visual acuity (BCVA) had improved significantly (p<0.05) and clinically (> 5 letters), as highlighted in the text.
The analysis of central macular thickness (CMT) at 12 months on optical coherence tomography disclosed that the poor and good responders reached CMT of 363 microns and of 359 microns, respectively. Despite being more than the cutoff for the upper level of normal CMT, as suggested by the Authors, for DME eyes a CMT of ~350um should be considered as a good outcome, as values inferior to this cut-off would indicate impending atrophy of the neurovascular tissue. As a validation of our approach, we referred to the latest Diabetic Retinopathy Clinical Research Network (DRCR.net) guidelines about persistent macular thickening after ranibizumab treatment, according to which CMT appeared to be a less important prognostic factor in DME outcomes. In fact, persistent macular edema was associated with similar long-term improvement in visual acuity showed by patients in which DME did not persist.2 Finally, we would like to specify that we analyzed data of included patients until 12-months follow-up; these patients did not conclude treatment for DME, and most of them continued to receive injections for their condition.
We perfectly agree that, along with CMT, other OCT biomarkers (as disorganization of the retinal inner layers, integrity of the ellipsoid zone and of the cone outer segment tips, presence of taut internal limiting membrane or epiretinal membrane, and vitreomacular traction) should be analyzed in order to predict the prognostic outcome of diabetic patients.3-4 A specific analysis of these parameters was beyond our purposes, but we will include them in a future more complete stepwise linear regression analysis of the data presented in the present study.
We listed the complications of treatment experienced by patients who underwent dexamethasone (DEX) implant, with particular attention to intraocular pressure increase as well as cataract worsening. These two are well-known side-effects of dexamethasone implant and their rate did not exceed the expectations in our study.5 Despite these complications, intravitreal steroids have shown a good safety profile in long-term prospective studies, especially in those cases when anti-VEGF are contraindicated, or fewer intravitreal injections regimen is required.
In conclusion, we kindly disagree with the conclusion of the Authors and we further demonstrated the usefulness of switching the therapeutic drug in diabetic patients non-responders to anti-VEGF the by replying to this letter.
References:
1. Cicinelli MV, Cavalleri M, Querques L, et al. Early response to ranibizumab predictive of functional outcome after dexamethasone for unresponsive diabetic macular oedema. Br J Ophthalmol 2017; http:/ dx. doi. org/ 10.1136/bjophthalmol-2017-310242.
2. Bressler SB, Ayala AR, Bressler NM, Melia M, Qin H, Ferris FL 3rd, Flaxel CJ, Friedman SM, Glassman AR, Jampol LM, Rauser ME; Diabetic Retinopathy Clinical Research Network. Persistent Macular Thickening After Ranibizumab Treatment for Diabetic Macular Edema With Vision Impairment. JAMA Ophthalmol. 2016 Mar;134(3):278-85. doi: 10.1001/jamaophthalmol.2015.5346.
3. Sun JK, Lin MM, Lammer J, Prager S, Sarangi R, Silva PS, Aiello LP. Disorganization of the retinal inner layers as a predictor of visual acuity in eyes with center-involved diabetic macular edema. JAMA Ophthalmol. 2014 Nov;132(11):1309-16.
4. Iacono P, Parodi MB, Scaramuzzi M, Bandello F. Morphological and functional changes in recalcitrant diabetic macular oedema after intravitreal dexamethasone implant. Br J Ophthalmol. 2016 Sep 13. pii: bjophthalmol-2016-308726. doi: 10.1136/bjophthalmol-2016-308726.
5. Boyer DS, Yoon YH, Belfort R Jr, et al; Ozurdex MEAD Study Group. Three-year, randomized, sham-controlled trial of dexamethasone intravitreal implant in patients with diabetic macular edema. 2014;121:1904-1914.
Dear Editor,
We read your article titled- Non-traumatic corneal perforations: aetiology, treatment and outcomes: with great interest. Corneal perforation is an acute ophthalmic emergency. This review describes the aetiology, plausible location and the multiple ways to approach the management of this condition in a very a systematic manner.
We do appreciate the organised mode of stratification and care of non- traumatic corneal perforation presented in the article. However, although the results are interesting, we feel that caution should be exercised when drawing conclusions from this data.
Initially, in results there are 127 eyes of 116 patients under the review. However, while describing the anatomical location of the perforation, only 102 eyes have been accounted for, with no records for the remaining 25 eyes. This would change the calculated p value significantly.
Similarly, where the initial treatments for perforations were being reviewed 133 eyes were mentioned as treated, thus including six extra unaccounted for eyes to the total. This would seriously jeopardise the authenticity of the calculated results.
Hence, there appears to be serious doubts regarding the validity of the conclusions of this review. A clearer and more detailed explanation or a recalculation of the results is warranted in this regard.
Thank you for your interest in our publication entitled "Preoperative aqueous humour flare values do not predict proliferative vitreoretinopathy in patients with rhegmatogenous retinal detachment".
As per request, we would like to provide more details on our protocol.
As described in our discussion, centre 1 used the mean of ten correct measurements making sure these measurements did not differ more than 2 standard deviations from each other. In centre 2, seven correct measurements were recorded of which the highest and lowest value were discarded leaving an average of five measurements. A correct measurement meant that the background readings did not differ more than 15% (indicated by the code ‘BG’ on the output) and that single “cell/C” measurements were replaced by an additional measurement. In addition, measurements with a small signal to noise ratio (indicated by the code ‘s/n’) were avoided as much as possible. However, with low flare values this was not always feasible. The flare meters were located in a room with blinds (centre 1) and a room without windows (centre 2); computer screens and lights were turned off during measurements. Both flare meters were calibrated monthly to assure correct readings. We therefore believe that the included mean values are artefact free.
Despite the exclusion of patients with additional conditions such as AMD, CRVO and preoperative PVR grade C or higher, we did end up with patients with a preopera...
Thank you for your interest in our publication entitled "Preoperative aqueous humour flare values do not predict proliferative vitreoretinopathy in patients with rhegmatogenous retinal detachment".
As per request, we would like to provide more details on our protocol.
As described in our discussion, centre 1 used the mean of ten correct measurements making sure these measurements did not differ more than 2 standard deviations from each other. In centre 2, seven correct measurements were recorded of which the highest and lowest value were discarded leaving an average of five measurements. A correct measurement meant that the background readings did not differ more than 15% (indicated by the code ‘BG’ on the output) and that single “cell/C” measurements were replaced by an additional measurement. In addition, measurements with a small signal to noise ratio (indicated by the code ‘s/n’) were avoided as much as possible. However, with low flare values this was not always feasible. The flare meters were located in a room with blinds (centre 1) and a room without windows (centre 2); computer screens and lights were turned off during measurements. Both flare meters were calibrated monthly to assure correct readings. We therefore believe that the included mean values are artefact free.
Despite the exclusion of patients with additional conditions such as AMD, CRVO and preoperative PVR grade C or higher, we did end up with patients with a preoperative flare value above 100 pc/ms. These measurements were accurate because they showed small SD’s (e.g. mean 263.8± SD 2.8; mean 196.5±SD 3.5; mean 162.0±SD 6.0) and flare was also visible upon slit lamp examination. Therefore, because these values do occur in patients with a rhegmatogenous retinal detachment we feel that inclusion of these measurements is mandatory.
However, excluding patients with a preoperative flare value above 100 pc/ms from our regression and ROC analyses – as is suggested by dr. Schaub and colleagues – did not significantly improve the results from either centre 1 or centre 2. Logistic regression centre 1: OR 1.013; p = 0.446, centre 2: OR 1.035; p = 0.028. Sensitivity and specificity at a cut-off of 15 pc/ms dropped to 78 and 39% in centre 1, and 36% and 77% in centre 2 (p = 0.051).
A possible explanation for the discrepancy with the previous reports is our low prevalence of postoperative PVR (7.5% and 6.2% respectively) compared to the previous reports. All previous reports included consecutive patients and found prevalences of 10.3%(1), 14.9%(2) and 20% (3). Both the positive predictive value (PPV) and the odds ratio (OR) are affected by the prevalence. This means that even with comparable sensitivity and specificity the PPV and the OR will be lower when the prevalence is lower. In addition, different reports used different definitions of postoperative PVR. We used reoperation due to epiretinal membranes and/or subretinal strands within six months of initial surgery, as did Schröder et al.(1) Hoerster et al. based their findings on PVR grade C at 3 months postoperatively. While ten patients developed PVR only four (6%) needed a reoperation.(2) It is unclear from the report whether all four patients had a flare value > 15 pc/ms but if this were the case this would give a PPV of 20% and OR of 8 instead of the reported 40% and 30. Conart et al. used PVR grade B and C at 6 months as the outcome. Moreover, they included 20% patients with preoperative PVR grade C which influenced the postoperative number of patients with PVR. Both studies included flare values > 100 pc/ms which confirms that high values are not uncommon.(2,3)
The predictive value of the flare value thus depends on the patient group that is targeted. Our results indicate that there is a large overlap in flare values which makes selecting those patient at high risk for developing postoperative PVR (according to our definition) inaccurate.(4) Dependent on the implications of a positive test result (flare value > 15pc/ms) we should decide whether a false discovery rate of 60-90% is acceptable.
We agree with dr. Schaub and collegues that identifying patients with an increased risk of PVR would be of great benefit in studies of the treatment of PVR by “enriching” the study population. Unfortunately, in our study, we have not been able to validate preoperative flare measurements for this purpose.
Recently, however, we have shown that postoperative flare measurements may have that potential (Mulder et al, non published data, presented at the NOG Maastricht, March 29 2017), and we encourage other groups to validate these findings.
References
1 Schroder S, Muether PS, Caramoy A, et al. Anterior chamber aqueous flare is a strong predictor for proliferative vitreoretinopathy in patients with rhegmatogenous retinal detachment. Retina 2012;32(1):38-42.
2 Hoerster R, Hermann MM, Rosentreter A, et al. Profibrotic cytokines in aqueous humour correlate with aqueous flare in patients with rhegmatogenous retinal detachment. Br.J.Ophthalmol. 2013;97(4):450-453.
3 Conart JB, Kurun S, Ameloot F, et al. Validity of aqueous flare measurement in predicting proliferative vitreoretinopathy in patients with rhegmatogenous retinal detachment. Acta Ophthalmol. 2016;.
4 Mulder VC, Kluft C, van Etten PG, et al. Higher vitreous concentrations of dabigatran after repeated oral administration. Acta Ophthalmol. 2017;.
I read with interest the article by Pawiroredjo et al1 which described an intervention programme to increase the cataract surgical rate in Suriname. I commend the team at the Suriname Eye Centre (SEC) for their efforts towards eliminating avoidable cataract blindness and visual impairment. The Suriname Rapid Assessment of Avoidable Blindness (2013-2014) survey showed that the proportion of eyes with a postoperative visual acuity <6/60 (poor outcome) was lowest in eyes operated at the SEC (8.5%), higher for the Cuban Mission Milagros (18.8%) and highest in surgeries performed by foreign humanitarian ophthalmic missions (33.3%).
In neighbouring Trinidad and Tobago, Persad and Bhola reported higher complication rates following cataract surgery performed by a foreign visiting team over a 2-week period compared to those done by local surgeons2. Despite a similar case mix, the visiting team had a sixfold higher vitreous loss rate and a fourfold higher overall surgical complication rate. The authors recommended careful screening of visiting surgical teams by relevant authorities. This supports Pawiroredjo’s suggestion of lowering complication rates and improving outcomes by regulating and limiting access of less experienced foreign ophthalmic teams to eye camps, where 50% of poor outcome was caused by intraoperative complications.
Suriname has achieved cataract surgical coverage (for all VA levels) of 90% in bilaterally blind or visually impaired individuals age...
I read with interest the article by Pawiroredjo et al1 which described an intervention programme to increase the cataract surgical rate in Suriname. I commend the team at the Suriname Eye Centre (SEC) for their efforts towards eliminating avoidable cataract blindness and visual impairment. The Suriname Rapid Assessment of Avoidable Blindness (2013-2014) survey showed that the proportion of eyes with a postoperative visual acuity <6/60 (poor outcome) was lowest in eyes operated at the SEC (8.5%), higher for the Cuban Mission Milagros (18.8%) and highest in surgeries performed by foreign humanitarian ophthalmic missions (33.3%).
In neighbouring Trinidad and Tobago, Persad and Bhola reported higher complication rates following cataract surgery performed by a foreign visiting team over a 2-week period compared to those done by local surgeons2. Despite a similar case mix, the visiting team had a sixfold higher vitreous loss rate and a fourfold higher overall surgical complication rate. The authors recommended careful screening of visiting surgical teams by relevant authorities. This supports Pawiroredjo’s suggestion of lowering complication rates and improving outcomes by regulating and limiting access of less experienced foreign ophthalmic teams to eye camps, where 50% of poor outcome was caused by intraoperative complications.
Suriname has achieved cataract surgical coverage (for all VA levels) of 90% in bilaterally blind or visually impaired individuals aged ≥50 years.3 This has been accomplished by training its local surgeons in phacoemulsification and strengthening ophthalmic services at the SEC, resulting in a self-sufficient and sustainable system. This is in line with WHO’s framework for strengthening health systems and use of cataract surgery as a proxy indicator for the provision of eye care services4. It could also explain the difference in surgical outcomes between visiting and local teams. Other Caribbean territories should follow the Suriname initiative to improve eye care services in the region.
References:
1. Pawiroredjo JC, Minderhoud J, Mans DRA, et al. Br J Ophthalmol 2017;101:89–93.
2. Persad S, Bhola R West Indian Med J 2010;Vol 59 (suppl. 3)
3. Minderhoud J, Pawiroredjo JC, Themen HCI, et al. Blindness and visual impairment in the Republic of Suriname. Ophthalmology 2015;122:2147–9.
4. World Health Organization Universal eye health: a global action plan 2014-2019 available at http://www.who.int/blindness/actionplan/en/
Early response to ranibizumab predictive of functional outcome after dexamethasone for unresponsive diabetic macular oedema
Dan Calugaru, Mihai Calugaru
Department of Ophthalmology, Univ of Medicine Cluj-Napoca/Romania
Re: Early response to ranibizumab predictive of functional outcome after dexamethasone for unresponsive diabetic macular oedema. Cicinelli et al. Br J Ophthalmol 2017; http: /dx.doi. org/ 10.1136/bjophthalmol-2017-310242.
Dear Editor
We would like to address several challenges that have arisen from the study by Cicinelli et al (1), which can be specifically summarized below.
1. The study was retrospectively conducted, with a selection bias attributable to the heterogeneity of the patients included, for example, six patients were affected by the type 1 diabetes mellitus; eighteen eyes were phakic; twenty seven eyes underwent cataract extraction and intraocular lens implant; and thirteen eyes received grid macular photocoagulation for diabetic macular oedema (DME) prior to ranibizumab (RNB).
2. After undergoing three loading-dose intravitreal injections of RNB performed at fixed 4-week intervals for the first 12 weeks, all the patients regardless of functional and anatomical characteristics, were shifted to dexamethasone implant (DEX implant 0.7 mg; Ozurdex; Allergan, Irvine, California, USA) continued at 4-month intervals until stable best-corrected visual acuity (BCVA) was reached. However, nothing was...
Early response to ranibizumab predictive of functional outcome after dexamethasone for unresponsive diabetic macular oedema
Dan Calugaru, Mihai Calugaru
Department of Ophthalmology, Univ of Medicine Cluj-Napoca/Romania
Re: Early response to ranibizumab predictive of functional outcome after dexamethasone for unresponsive diabetic macular oedema. Cicinelli et al. Br J Ophthalmol 2017; http: /dx.doi. org/ 10.1136/bjophthalmol-2017-310242.
Dear Editor
We would like to address several challenges that have arisen from the study by Cicinelli et al (1), which can be specifically summarized below.
1. The study was retrospectively conducted, with a selection bias attributable to the heterogeneity of the patients included, for example, six patients were affected by the type 1 diabetes mellitus; eighteen eyes were phakic; twenty seven eyes underwent cataract extraction and intraocular lens implant; and thirteen eyes received grid macular photocoagulation for diabetic macular oedema (DME) prior to ranibizumab (RNB).
2. After undergoing three loading-dose intravitreal injections of RNB performed at fixed 4-week intervals for the first 12 weeks, all the patients regardless of functional and anatomical characteristics, were shifted to dexamethasone implant (DEX implant 0.7 mg; Ozurdex; Allergan, Irvine, California, USA) continued at 4-month intervals until stable best-corrected visual acuity (BCVA) was reached. However, nothing was stated as to whether there were patients with complete retinal dryness at week 12 and if so, why they were switched to dexamethasone implant.
3. In the assessment of the final results of this study we 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 final outcomes of this series were unsatisfactory. Specifically, despite a significant mean gain of 5.6 Early Treatment Diabetic Retinopathy Study (ETDRS) letters in BCVA score in poorly responding patients and an insignificant improvement of 2.1 ETDRS letters in patients with good visual response, the central macular thickness (CMT) decreased significantly to 363.6 microns and reduced insignificantly to 359 microns, in the poor and good responders, respectively. Of note, the both CMT values were more than the cutoff for the upper level of normal CMT [3], highlighting unresolved DME. Moreover, seven eyes developed intraocular pressure =/> 20 mm Hg, cataract progression was observed in nine among the phakic eyes (50%) during the study period, and two patients underwent cataract extraction after the dexamethasone implant. Importantly, persistence of unresolved macular oedema can permanently damage the outer retinal layers, leading to retinal fibrosis and macular atrophy, indicating that the disease process is still active and progressive, requiring further treatment with antiangiogenic agents.
4. As far as the potential prognosticatours of clinical outcome after dexamethasone implant are concerned, the following baseline characteristics should have been considered and included in a stepwise linear regression analysis along with those already presented, namely the subfoveal choroidal thickness, the qualitative status of the 4 outer retinal layers, the vitreoretinal interface abnormalities (vitreomacular adhesion/traction and epiretinal membrane), the diabetic retinopathy severity, the presence of macular ischemia on fluorescein angiography, and the duration of DME prior to therapy.
5. The specific anti-VEGF drugs (bevacizumab [Avastin; Genentech, South San Francisco, California, USA)/ranibizumab [Lucentis, Genentech]/aflibercept [Eylea; Regeneron Pharmaceuticals Inc, Tarrytown, New York, USA]) represent the front-line therapy for the treatment of DME but only the VEGF inhibition may not be sufficient to decrease inflammatory response. Therefore, addition of a non-specific anti-VEGF substance, ie. a corticosteroid implant, is mandatory. Both groups of anti-VEGF substances provide similar rates of vision improvement but with superior anatomic outcomes and fewer injections in the corticosteroid implant-treated eyes. However, more patients receiving the corticosteroid implant lose vision mainly due to cataract [4].
Altogether, the results of this study can not be validated and extrapolated because a stepwise linear regression analysis of the potential predictors of functional outcome was not carried out. Regardless of the anti-VEGF agents employed (bevacizumab/ranibizumab/aflibercept/ corticosteroid), the efficacy of therapy depends primarily on the promptness of the therapy after DME diagnosis [4,5].
References
1. Cicinelli MV, Cavalleri M, Querques L, et al. Early response to ranibizumab predictive of functional outcome after dexamethasone for unresponsive diabetic macular oedema. Br J Ophthalmol 2017; http:/ dx. doi. org/ 10.1136/bjophthalmol-2017-310242.
2. Freund KB, Korobelnik JF, Devenyi R, et al. Treat-and-extend regimens with anti-VEGF agents in retinal diseases. Retina 2015;35(8):1489-1506.
3. Gover S, Murthy RK, Brar VS, Chalam KV.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(2):175-176.
5. Calugaru D, Calugaru M. Comments to: Long-term efficacy and safety of intravitreal dexamethasone implant for the treatment of diabetic macular edema. Eur J Ophthalmol 2016;26(6):171-172.
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 study by Salowi and colleagues,[1] analysing risk factors for posterior capsular rupture (PCR) in over 150,000 cataract operations across Malaysia. Many of the significant risk factors were expected and well-recognised, such as junior surgeon or pseudoexfoliation. An interesting finding was increased PCR in males, with odd ratio 1.11 (95% confidence interval 1.04 to 1.17).
Male gender has been found to be a risk factor for PCR in other large retrospective studies. The Cataract National Dataset of 55,567 cataract operations across 12 National Health Service Trusts in the UK found male gender to have an adjusted odds ratio of 1.28 (95% CI 1.13-1.45).[2] We recently reviewed 62,994 cataract operations performed at Moorfields, showing male gender as a significant risk for PCR, with OR 1.490 (95% CI 1.274–1.741).[3] This risk was similar to junior surgeon (OR 1.483) or prior intravitreal injection (OR 1.664), an increasingly acknowledged predictor of complicated surgery.
The reasons for increased PCR in male patients is unclear. Males are significantly more likely to take tamsulosin, an alpha receptor blocker used in the treatment of benign prostatic hypertrophy. This can lead to poor pupillary dilation and intraoperative floppy iris syndrome (IFIS).[4] Although this can be effectively managed with intracameral phenylephrine, iris hooks or Malyugin ring, it remains a risk factor for PCR. Furthermore, males are more likely to be aff...
Show MoreDear sir/maam
I whole heartedly appreciate the work conducted by Chan Yun Kim et al in studying the treatment patterns and medication adherence of patients with glaucoma in South Korea.This study concluded that medication non adherence was seen more commonly in males , increased daily number of administration and increase in the number of eyedrops. We have also conducted a similar study at our centre in North India and would like to share our results .Our results are in agreement to the work conducted by Chan Yun Kim stating that increased number of instillation and increased number of eyedrops contribute significantly to medication non adherence. However, in our study we also found that medication adherence varies in different severity grades of glaucoma with severe stages being significantly more adherent than mild to moderate stages of glaucoma.Additionally, there was no difference found in medication adherence among males or females.
We again express our gratitude to the researcher in enlightening our minds regarding medication adherence in South Korean population.
Dear editor.
We thank Sarmad et al. for their interest in our publication. Our study is a retrospective review of several variables regarding non-traumatic corneal perforations (1). In handling clinical records for a retrospective analysis, missing variables represent a common problem. In relation to the location of corneal perforation, information was not available in 25 eyes thus the number does not match. Hence, in consideration of this inevitable flaw we decided not to include the anatomical location of perforation into the model presented in the manuscript, therefore all the variables included in this statistical model had no missing values.
Clinical treatment of corneal perforation is often complex and a single intervention may not address the patient full pathology, therefore more than one treatment is frequently used. (2) This explains the increased number of initial treatments in the first clinical intervention, one example of this scenario are the patients needing simultaneous tectonic penetrating keratoplasty to restore ocular integrity and concurrent amniotic membrane transplantation to aid in the control of ocular surface. (2)(3)
These two situations might not be precise in our manuscript, but we take the opportunity of this letter to clarify them. However, that is unquestionably far from compromising the validity of the conclusions. Definitely, as any retrospective study, and as we mention in the discussion of our article, there are li...
Show MoreWe warmly thank Calugaru D and associates for their correspondence regarding our article entitled " Early response to ranibizumab predictive of functional outcome after dexamethasone for unresponsive diabetic macular oedema".1
Show MoreWe agree with them about some of the challenges concerning our study. As we have acknowledged in the limitation section of our article, our study is limited by several biases, as its design was retrospective. In particular, patients selection and follow-up represented some of the major flaws in our study. We collected data about patients switched to dexamethasone for different reasons; some patients were treatment-naïve, other had already undergone treatments for diabetic macular edema (DME). No one disclosed any feature of chronic long-standing DME; all of them received prompt therapy after DME diagnosis.
Some of them showed a good response to ranibizumab loading-dose, with satisfying reduction of macular thickness after the injections. Nevertheless, no patient disclosed a completely dry macula after the anti-vascular endothelial growth factor (VEGF) loading-dose.
As far as it regards the final functional and anatomical gain at the end of the follow-up, the Authors state that the outcomes of this series were unsatisfactory. However, in the non-responders group, despite initial poor results, the best-corrected visual acuity (BCVA) had improved significantly (p<0.05) and clinically (> 5 letters), as highlighted in the...
Dear Editor,
We read your article titled- Non-traumatic corneal perforations: aetiology, treatment and outcomes: with great interest. Corneal perforation is an acute ophthalmic emergency. This review describes the aetiology, plausible location and the multiple ways to approach the management of this condition in a very a systematic manner.
We do appreciate the organised mode of stratification and care of non- traumatic corneal perforation presented in the article. However, although the results are interesting, we feel that caution should be exercised when drawing conclusions from this data.
Initially, in results there are 127 eyes of 116 patients under the review. However, while describing the anatomical location of the perforation, only 102 eyes have been accounted for, with no records for the remaining 25 eyes. This would change the calculated p value significantly.
Similarly, where the initial treatments for perforations were being reviewed 133 eyes were mentioned as treated, thus including six extra unaccounted for eyes to the total. This would seriously jeopardise the authenticity of the calculated results.
Hence, there appears to be serious doubts regarding the validity of the conclusions of this review. A clearer and more detailed explanation or a recalculation of the results is warranted in this regard.
Thank you for your interest in our publication entitled "Preoperative aqueous humour flare values do not predict proliferative vitreoretinopathy in patients with rhegmatogenous retinal detachment".
As per request, we would like to provide more details on our protocol.
As described in our discussion, centre 1 used the mean of ten correct measurements making sure these measurements did not differ more than 2 standard deviations from each other. In centre 2, seven correct measurements were recorded of which the highest and lowest value were discarded leaving an average of five measurements. A correct measurement meant that the background readings did not differ more than 15% (indicated by the code ‘BG’ on the output) and that single “cell/C” measurements were replaced by an additional measurement. In addition, measurements with a small signal to noise ratio (indicated by the code ‘s/n’) were avoided as much as possible. However, with low flare values this was not always feasible. The flare meters were located in a room with blinds (centre 1) and a room without windows (centre 2); computer screens and lights were turned off during measurements. Both flare meters were calibrated monthly to assure correct readings. We therefore believe that the included mean values are artefact free.
Despite the exclusion of patients with additional conditions such as AMD, CRVO and preoperative PVR grade C or higher, we did end up with patients with a preopera...
Show MoreI read with interest the article by Pawiroredjo et al1 which described an intervention programme to increase the cataract surgical rate in Suriname. I commend the team at the Suriname Eye Centre (SEC) for their efforts towards eliminating avoidable cataract blindness and visual impairment. The Suriname Rapid Assessment of Avoidable Blindness (2013-2014) survey showed that the proportion of eyes with a postoperative visual acuity <6/60 (poor outcome) was lowest in eyes operated at the SEC (8.5%), higher for the Cuban Mission Milagros (18.8%) and highest in surgeries performed by foreign humanitarian ophthalmic missions (33.3%).
In neighbouring Trinidad and Tobago, Persad and Bhola reported higher complication rates following cataract surgery performed by a foreign visiting team over a 2-week period compared to those done by local surgeons2. Despite a similar case mix, the visiting team had a sixfold higher vitreous loss rate and a fourfold higher overall surgical complication rate. The authors recommended careful screening of visiting surgical teams by relevant authorities. This supports Pawiroredjo’s suggestion of lowering complication rates and improving outcomes by regulating and limiting access of less experienced foreign ophthalmic teams to eye camps, where 50% of poor outcome was caused by intraoperative complications.
Suriname has achieved cataract surgical coverage (for all VA levels) of 90% in bilaterally blind or visually impaired individuals age...
Show MoreEarly response to ranibizumab predictive of functional outcome after dexamethasone for unresponsive diabetic macular oedema
Dan Calugaru, Mihai Calugaru
Department of Ophthalmology, Univ of Medicine Cluj-Napoca/Romania
Re: Early response to ranibizumab predictive of functional outcome after dexamethasone for unresponsive diabetic macular oedema. Cicinelli et al. Br J Ophthalmol 2017; http: /dx.doi. org/ 10.1136/bjophthalmol-2017-310242.
Dear Editor
Show MoreWe would like to address several challenges that have arisen from the study by Cicinelli et al (1), which can be specifically summarized below.
1. The study was retrospectively conducted, with a selection bias attributable to the heterogeneity of the patients included, for example, six patients were affected by the type 1 diabetes mellitus; eighteen eyes were phakic; twenty seven eyes underwent cataract extraction and intraocular lens implant; and thirteen eyes received grid macular photocoagulation for diabetic macular oedema (DME) prior to ranibizumab (RNB).
2. After undergoing three loading-dose intravitreal injections of RNB performed at fixed 4-week intervals for the first 12 weeks, all the patients regardless of functional and anatomical characteristics, were shifted to dexamethasone implant (DEX implant 0.7 mg; Ozurdex; Allergan, Irvine, California, USA) continued at 4-month intervals until stable best-corrected visual acuity (BCVA) was reached. However, nothing was...
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.
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