I have read with interest the paper by Fabian ID et al. “Travel burden and clinical presentation of retinoblastoma”[1]. I acknowledge the efforts conducted by the authors to build a retinoblastoma knowledge based on a large consortium for the first time. Many publications have agreed that the underprivileged socioeconomic situations affect the presentation and outcome of retinoblastoma patients[2, 3]. The measures used in most publications, including the one by Fabian ID et al., are national-level measures. Such socioeconomic measures on the country level affect the roads and travel quality beside family and healthcare giver education and training. A better measure in such cases is an individual level for each family. In developing countries, a vast gap presents between inhabitants letting a country-level measure, not representative. As mentioned in a glimpse in the paper, patients can spend a long time orbiting multiple physicians before targeting the oncology center. On the other side, people with higher economic status can get better healthcare and travel longer distances comfortably and present to centers with early stages.
Furthermore, Figure 2 shows interestingly similar small catchment areas in Africa; this raised a question on the data that were used for drawing the figure; is it individualized for each center? Additionally, if the analysis depended on the permanent address.
Egypt’s major pediatric oncology center, which was included in the study, cover...
I have read with interest the paper by Fabian ID et al. “Travel burden and clinical presentation of retinoblastoma”[1]. I acknowledge the efforts conducted by the authors to build a retinoblastoma knowledge based on a large consortium for the first time. Many publications have agreed that the underprivileged socioeconomic situations affect the presentation and outcome of retinoblastoma patients[2, 3]. The measures used in most publications, including the one by Fabian ID et al., are national-level measures. Such socioeconomic measures on the country level affect the roads and travel quality beside family and healthcare giver education and training. A better measure in such cases is an individual level for each family. In developing countries, a vast gap presents between inhabitants letting a country-level measure, not representative. As mentioned in a glimpse in the paper, patients can spend a long time orbiting multiple physicians before targeting the oncology center. On the other side, people with higher economic status can get better healthcare and travel longer distances comfortably and present to centers with early stages.
Furthermore, Figure 2 shows interestingly similar small catchment areas in Africa; this raised a question on the data that were used for drawing the figure; is it individualized for each center? Additionally, if the analysis depended on the permanent address.
Egypt’s major pediatric oncology center, which was included in the study, covers the whole country region, and about 10 % of its patients are traveling from other countries to get the treatment in the hospital[4], however, this reality was not reflected on the figure. Beside, In the journey of treatment, patients acquire a temporary or interim residence near the hospital due to the hard return to the permanent residence. In Europe, borders are open, cities are connected with high-speed trains, with 420 kilometers can be traveled in 2-3 hours, while in Africa, 185 kilometers can require a day with a significant part of the distance on foot and months for getting a visa if crossing borders is required. Such factors can bias the results.
So, further clarification is required for this figure to answer these question.
References
1. Fabian ID, Stacey AW, Foster A, et al (2020) Travel burden and clinical presentation of retinoblastoma: analysis of 1024 patients from 43 African countries and 518 patients from 40 European countries. Br J Ophthalmol bjophthalmol-2020-316613. https://doi.org/10.1136/bjophthalmol-2020-316613
2. Canturk S, Qaddoumi I, Khetan V, et al (2010) Survival of retinoblastoma in less-developed countries impact of socioeconomic and health-related indicators. Br J Ophthalmol 94:1432–6. https://doi.org/10.1136/bjo.2009.168062
3. Aziz H a, Lasenna CE, Vigoda M, et al (2012) Retinoblastoma treatment burden and economic cost: impact of age at diagnosis and selection of primary therapy. Clin Ophthalmol 6:1601–6. https://doi.org/10.2147/OPTH.S33094
4. El Zomor H, Nour R, Alieldin A, et al (2015) Clinical presentation of intraocular retinoblastoma; 5-year hospital-based registry in Egypt. J Egypt Natl Canc Inst 27:195–203. https://doi.org/10.1016/j.jnci.2015.09.002
We thank Alfaar for their comment on our paper titled: “Travel burden and clinical presentation of retinoblastoma: analysis of 1024 patients from 43 African countries and 518 patients from 40 European contries”.[1]
In our paper, we compared the stage of presentation of newly diagnosed retinoblastoma patients from African and European countries and investigated possible associations to the travel distance from home to treatment centre. Our findings suggest that treatment centres in African countries serve patients that reside, on average, in closer proximity to the treatment center than in Europe (186 km average distance travelled in Africa compared to an average distance travelled of 422 km in Europe). In reply to Alfaar’s comment, to produce these numbers, we calculated the average travel distance in a country and then calculated the mean of averages in a continent and compared Africa to Europe.
The red circles in Figure 2 in our original paper,[1] representing the mean travel distance in a continent, were superimposed on each centre on a scaled map. All red circles in Africa are similar in size (i.e. radius of 186 km) and all in Europe are similar (i.e. radius of 422 km).
We agree with Alfaar that our analysis has several limitations, some of which are mentioned in our paper and some, rightfully, in his eLetter. In a study, in which patients from over 80 countries in two continents are included, one cannot take into account all considerations, especiall...
We thank Alfaar for their comment on our paper titled: “Travel burden and clinical presentation of retinoblastoma: analysis of 1024 patients from 43 African countries and 518 patients from 40 European contries”.[1]
In our paper, we compared the stage of presentation of newly diagnosed retinoblastoma patients from African and European countries and investigated possible associations to the travel distance from home to treatment centre. Our findings suggest that treatment centres in African countries serve patients that reside, on average, in closer proximity to the treatment center than in Europe (186 km average distance travelled in Africa compared to an average distance travelled of 422 km in Europe). In reply to Alfaar’s comment, to produce these numbers, we calculated the average travel distance in a country and then calculated the mean of averages in a continent and compared Africa to Europe.
The red circles in Figure 2 in our original paper,[1] representing the mean travel distance in a continent, were superimposed on each centre on a scaled map. All red circles in Africa are similar in size (i.e. radius of 186 km) and all in Europe are similar (i.e. radius of 422 km).
We agree with Alfaar that our analysis has several limitations, some of which are mentioned in our paper and some, rightfully, in his eLetter. In a study, in which patients from over 80 countries in two continents are included, one cannot take into account all considerations, especially not at patient (e.g. socioeconomic status) or centre level, as Alfaar suggests.
Alfaar, in the eLetter, indicates, “Egypt’s major paediatric oncology centre, which was included in the study, covers the whole country region”. According to our study,[1] In 2017, more than 100 new retinoblastoma patients presented to this centre. The calculated average travel distance from home to the centre was 178 km (±117), similar to the average in the continent for all African countries. Noteworthy, the western as well as the southern borders of Egypt are each more than 1,000 km long (surface area of more than 1 million km2). The raw data at country level is available at https://zenodo.org/record/3727687#.X4_LgdAzbIU.[2]
Concerning patients traveling abroad to seek medical care, these cases were excluded from the current analysis in both Europe and Africa, but were included in a separate report, titled: “International travel to obtain medical treatment for primary retinoblastoma: a global cohort study”.[3]
The access to care by children with retinoblastoma in Africa, as demonstrated by the estimated proportion of new retinoblastoma cases seen by treatment centres in Europe versus Africa of over 100% to less than 50%,[1] is compromised due to a variety of factors. A multicentre collaboration,[4,5] including most retinoblastoma treatment centres in Europe and Africa, despite its weaknesses, is of importance to highlight the huge gap in access to care in different regions of the world.
References
1 Fabian ID, Stacey AW, Foster A, et al. Travel burden and clinical presentation of retinoblastoma: Analysis of 1024 patients from 43 African countries and 518 patients from 40 European countries. Br J Ophthalmol Published Online First: 2020. doi:10.1136/bjophthalmol-2020-316613
2. Fabian ID, Stacey A, Foster A, Kivelä TT, Munier FL, Cassoux N, & Bowman RJC. (2020). Global Retinoblastoma Presentation 2017 data, on behalf of the Global Retinoblastoma Study Group [Data set]. Zenodo. http://doi.org/10.5281/zenodo.3727687
3. Bowman R, Foster A, Stacey A, et al. International travel to obtain medical treatment for primary retinoblastoma: a global cohort study. Int J cancer 2020; Online ahead of print. doi:10.1002/ijc.33350
4 Global Retinoblastoma Study Group. Global Retinoblastoma Presentation and Analysis by National Income Level. JAMA Oncol 2020;6:1–12. doi:10.1001/jamaoncol.2019.6716
5 Fabian ID, Stacey AW, Bowman R, et al. Retinoblastoma management during the COVID-19 pandemic: A report by the Global Retinoblastoma Study Group including 194 centers from 94 countries. Pediatr. Blood Cancer. 2020. doi:10.1002/pbc.28584
Reply to the comment on: “Influence of corneal guttae and nuclear cataract on contrast sensitivity”
We thank Sanjay V Patel for the comments. Patients with Fuchs endothelial corneal dystrophy (FECD) are known to have reduced contrast sensitivity due to corneal edema and guttae. Before the introduction of endothelial keratoplasty, penetrating keratoplasty had been performed mainly in patients with advanced FECD and clinically significant corneal edema. However, as endothelial keratoplasty procedures such as Descemet membrane endothelial keratoplasty can bring excellent visual acuity outcomes, surgery can be performed earlier and even in cases without any clinical corneal edema. Therefore, it has become even more important to detect the causes of visual impairment in patients with FECD. In our retrospective study, we enrolled FECD patients with >5 mm of confluent guttae and no corneal edema (modified Krachmer grade 5). When analyzed by Scheimpflug tomography, our FECD patients showed no difference in the central corneal thickness and corneal volume when compared to the control group of cataract patients without any corneal pathologies.1 Recently, Sun et al. presented a new method to detect subclinical corneal edema in patients with FECD.2,3 The authors analyzed three Scheimpflug tomography pachymetry map and posterior elevation map patterns to detect subclinical edema in FECD patients: loss of regular isopachs, displacement of the thinnest point of the cornea, and...
Reply to the comment on: “Influence of corneal guttae and nuclear cataract on contrast sensitivity”
We thank Sanjay V Patel for the comments. Patients with Fuchs endothelial corneal dystrophy (FECD) are known to have reduced contrast sensitivity due to corneal edema and guttae. Before the introduction of endothelial keratoplasty, penetrating keratoplasty had been performed mainly in patients with advanced FECD and clinically significant corneal edema. However, as endothelial keratoplasty procedures such as Descemet membrane endothelial keratoplasty can bring excellent visual acuity outcomes, surgery can be performed earlier and even in cases without any clinical corneal edema. Therefore, it has become even more important to detect the causes of visual impairment in patients with FECD. In our retrospective study, we enrolled FECD patients with >5 mm of confluent guttae and no corneal edema (modified Krachmer grade 5). When analyzed by Scheimpflug tomography, our FECD patients showed no difference in the central corneal thickness and corneal volume when compared to the control group of cataract patients without any corneal pathologies.1 Recently, Sun et al. presented a new method to detect subclinical corneal edema in patients with FECD.2,3 The authors analyzed three Scheimpflug tomography pachymetry map and posterior elevation map patterns to detect subclinical edema in FECD patients: loss of regular isopachs, displacement of the thinnest point of the cornea, and presence of posterior surface depression may help identify subclinical corneal edema more accurately in patients with FECD. In our study, the loss of regular isopachs (12/25 [48%] vs. 4/25 [16%]), the displacement of the thinnest point of the cornea (11/25 [44%] vs. 1/25 [4%]), and the posterior surface depression (13/25 [52%] vs. 8/25 [32%]) could be found more frequently in FECD patients, than in the control group without corneal pathology. Eleven of the 25 FECD patients (44%) met at least two of the three criteria, implying the presence of a subclinical corneal edema. However, the preoperative MARS letter contrast sensitivity of these 11 patients (contrast sensitivity: 0.98 ± 0.13 logCS) did not show any statistically significant difference compared to that of the other 14 FECD patients (contrast sensitivity: 1.02 ± 0.09 logCS; p=0.47) in whom the aforementioned criteria were not met. Interestingly, two of the three criteria were also met in 4 cases (16%) of the control group. Indeed, future studies should also include the analysis of these patterns when assessing the contrast sensitivity in FECD patients.
1Augustin VA, Weller JM, Kruse FE, Tourtas T. Influence of corneal guttae and nuclear cataract on contrast sensitivity. Br J Ophthalmol 2020.
2Sun SY, Wacker K, Baratz KH, Patel SV. Determining Subclinical Edema in Fuchs Endothelial Corneal Dystrophy. Revised Classification using Scheimpflug Tomography for Preoperative Assessment. Ophthalmology 2019;126:195-204.
3Patel SV, Hodge DO, Treichel EJ, Spiegel MR, Baratz KH. Predicting the Prognosis of Fuchs Endothelial Corneal Dystrophy by using Scheimpflug Tomography. Ophthalmology 2020;127:315-323.
McCann et al. reported factors of the associations with intraocular pressure (IOP) and circumpapillary retinal nerve fibre layer (cRNFL) thickness (1). Increased IOP and reduced cRNFL were associated with increased age, myopic refractive error, male sex and hypertension. In addition, Alzheimer's disease was associated with thinner average global cRNFL, and Parkinson's disease (PD) and current smoking status were associated with thicker average global cRNFL, and I present recent information regarding their study in patients with PD.
Murueta-Goyena et al. reported the association between the changes of retinal thickness and their predictive value as biomarkers of disease progression in idiopathic PD (2). The authors used macular ganglion-inner plexiform layer complex (mGCIPL) and peripapillary retinal nerve fiber layer (pRNFL) thickness reduction rates, and the Montreal Cognitive Assessment (MoCA) questionnaire was also applied. The adjusted relative risks of lower parafoveal mGCIPL and pRNFL thickness at baseline for an increased risk of cognitive decline at 3 years significantly increased. This means that reduced retinal thickness is a risk factor of cognitive impairment in patients with PD. McCann et al. did not evaluate cRNFL in PD patients with cognitive impairment, and I suppose that progression of cognitive impairment in patients with PD might accelerate reduction of average global cRNFL.
Second, Sung et al. also investigated the association be...
McCann et al. reported factors of the associations with intraocular pressure (IOP) and circumpapillary retinal nerve fibre layer (cRNFL) thickness (1). Increased IOP and reduced cRNFL were associated with increased age, myopic refractive error, male sex and hypertension. In addition, Alzheimer's disease was associated with thinner average global cRNFL, and Parkinson's disease (PD) and current smoking status were associated with thicker average global cRNFL, and I present recent information regarding their study in patients with PD.
Murueta-Goyena et al. reported the association between the changes of retinal thickness and their predictive value as biomarkers of disease progression in idiopathic PD (2). The authors used macular ganglion-inner plexiform layer complex (mGCIPL) and peripapillary retinal nerve fiber layer (pRNFL) thickness reduction rates, and the Montreal Cognitive Assessment (MoCA) questionnaire was also applied. The adjusted relative risks of lower parafoveal mGCIPL and pRNFL thickness at baseline for an increased risk of cognitive decline at 3 years significantly increased. This means that reduced retinal thickness is a risk factor of cognitive impairment in patients with PD. McCann et al. did not evaluate cRNFL in PD patients with cognitive impairment, and I suppose that progression of cognitive impairment in patients with PD might accelerate reduction of average global cRNFL.
Second, Sung et al. also investigated the association between retinal thinning and cognitive impairment in patients with PD (3). There were significant reductions in the thickness of average, temporal, and inferior pRNFL and overall mGCIPL in patients with PD, and the MoCA score was significantly associated with mGCIPL thinning. As the thinning of the mGCIPL was also significantly associated with the volumetric parameters of some brain structures, the relationship between retinal thickness and brain structures in patients with PD should be comprehensively evaluated with special reference to the level of cognitive impairment.
Finally, Matlach et al. reported that thinning of some retinal layers of the ipsilateral eye was observed in the most-affected body side of PD patients (4). In addition, thickness of pRNFL and mGCIPL did not correlate to the severity of PD. As Murueta-Goyena et al. reported that there was no significant association between retinal thickness and motor deterioration (2), the discrepancy in the relationship of cognitive decline and motor deterioration with retinal thickness might be related to the lack of relationship between retinal thickness and the severity of PD.
References
1. McCann P, Hogg R, Wright DM, et al. Intraocular pressure and circumpapillary retinal nerve fibre layer thickness in the Northern Ireland Cohort for the Longitudinal Study of Ageing (NICOLA): distributions and associations. Br J Ophthalmol. 2020 Jul 30 doi: 10.1136/bjophthalmol-2020-316499 [Epub ahead of print]
2. Murueta-Goyena A, Del Pino R, Galdós M, et al. Retinal thickness predicts the risk of cognitive decline in Parkinson's disease. Ann Neurol 2020 Oct 24 doi: 10.1002/ana.25944 [Epub ahead of print]
3. Sung MS, Choi SM, Kim J, et al. Inner retinal thinning as a biomarker for cognitive impairment in de novo Parkinson's disease. Sci Rep 2019;9:11832.
4. Matlach J, Wagner M, Malzahn U, et al. Retinal changes in Parkinson's disease and glaucoma. Parkinsonism Relat Disord 2018 Nov;56:41-46.
Corneal graft rejection following vaccination was first reported in 1988 by T L Steinemann, B H Koffler and C D Jennings [1]. This article is missing from Table 1, “Summary of reported cases of corneal graft rejection”. As it is the first published study to describe this temporal association, it merits mention.
In regards to preventative measures, we recommend thoroughly counseling patients with grafts. They should be educated on the salient warning signs of rejection including pain, redness, blurred vision, and irritation. Patients should also be informed that COVID-19 vaccination may pose a risk to the viability of their corneal grafts. We recommend prophylactically increasing topical steroids for 3-4 weeks around the time of each vaccination.
References
1. Steinemann TL, Koffler BH, Jennings CD. Corneal allograft rejection following immunization. Am J Ophthalmol. 1988 Nov 15;106(5):575-8. doi: 10.1016/0002-9394(88)90588-0. PMID: 3056015.
Atik et al (BJOhttps://bjo.bmj.com/content/105/5/602) have done an excellent job of summarizing the current state of the art for conducting health economic evaluations in ophthalmology. Not surprisingly, however, such tools and techniques were originally designed to address broader questions of healthcare funding and resource allocation across many disparate clinical areas. As such, the general use case was very far removed from ophthalmology. This is relevant as a central component is the calculation of the utility parameters used, particularly in cost-effectiveness calculations (1). At present, the standard default utility measure remains the EQ5D, which does not prima facie include a vision specific domain (2). Rather, a “Vision Bolt-On” to the EQ5D which asks patients whether they “Have no problems seeing”; “Have some problem seeing”; or “Have extreme problems seeing” is proposed for increasing the precision of the utility score derived from patients for ophthalmic interventions (3). Unfortunately, the “Vision Bolt On” while theoretically increasing the discriminating power of the EQ-5D has not been widely adopted in economic evaluations conducted in ophthalmology (3-4). Moreover, as currently configured, the “Vision Bolt On” questions fail to adequately account for the clinical differences, say between central or fine reading vision which may be more relevant in patients with age-related macular degeneration, versus...
Atik et al (BJOhttps://bjo.bmj.com/content/105/5/602) have done an excellent job of summarizing the current state of the art for conducting health economic evaluations in ophthalmology. Not surprisingly, however, such tools and techniques were originally designed to address broader questions of healthcare funding and resource allocation across many disparate clinical areas. As such, the general use case was very far removed from ophthalmology. This is relevant as a central component is the calculation of the utility parameters used, particularly in cost-effectiveness calculations (1). At present, the standard default utility measure remains the EQ5D, which does not prima facie include a vision specific domain (2). Rather, a “Vision Bolt-On” to the EQ5D which asks patients whether they “Have no problems seeing”; “Have some problem seeing”; or “Have extreme problems seeing” is proposed for increasing the precision of the utility score derived from patients for ophthalmic interventions (3). Unfortunately, the “Vision Bolt On” while theoretically increasing the discriminating power of the EQ-5D has not been widely adopted in economic evaluations conducted in ophthalmology (3-4). Moreover, as currently configured, the “Vision Bolt On” questions fail to adequately account for the clinical differences, say between central or fine reading vision which may be more relevant in patients with age-related macular degeneration, versus the loss of peripheral retinal photoreceptors on a patient’s navigation vision such as in glaucoma. Additional attempts designed to extend the “Vision Bolt On” including the Glaucoma Utility Index (GUI) to increase such discriminating abilities, however, have concluded that more research on the link between utility measures and precise clinical parameters is needed to better capture the subtle components of a patient’s vision on their overall global utility score (5). The time is, therefore, ripe for a concerted research effort to develop and validate such a truly relevant utility measure tailored to ophthalmic interventions.
Word Count: 300
References:
1. Smith AF, Brown GC. Understanding cost-effectiveness: a detailed review, Brit-J-Ophthalmol, 2000; 84: 794-798
3. Yang Y, Rowen D, Brazier J, et al. An exploratory study to test the impact on three "bolt-on" items to the EQ-5D. Value Health 2015 Jan;18(1):52-60.
4. Luo N, Wang X, Ang M, et al. A Vision "Bolt-On" Item Could Increase the Discriminatory Power of the EQ-5D Index Score. Value Health 2015;18(8):1037‐1042
5. Burr JM, Kilonzo M, Vale L, et al. Developing a preference-based Glaucoma Utility Index using a discrete choice experiment. Optom Vis Sci. 2007;84(8):797‐808
We welcome the recent meta-analysis by Hedengran and co-workers in the British Journal of Ophthalmology (BJO).1 This study compared the efficacy and safety of benzalkonium chloride (BAK)-preserved eye drops with alternatively preserved (AP) and preservative-free (PF) eye drops. The meta-analysis was conducted on 16 studies that range from 15 days to 6 months of study duration. Change in IOP in BAK vs AP and PF groups was meta-analysed as the primary outcome. Conjunctival hyperaemia, ocular hyperaemia, total ocular adverse effects (AE), and TBUT were also meta-analysed. The authors found no evidence of significant change in IOP and conjunctival hyperaemia between BAK vs AP and PF treatment groups. The authors concluded that the main reason for detecting no clinical differences between the groups was related to the lack of long-term clinical studies on the safety of BAK vs AP and PF eye drops. We are in consensus with Kontas AG et al., comments on the deficiencies of this meta-analysis.
We do not agree to the conclusion, “BAK-containing and PF medications do not differ with respect to tolerability and therapy outcome”. We would like to direct the authors and readers to our recently published study in the journal, Clinical and Experimental Ophthalmology (CEO), which involved the randomised evaluation of the inflammatory effects of PF vs BAK and PF vs polyquad (PQ)-preserved eye drops in naïve glaucomatous patients over the period of 24 months.2 We p...
We welcome the recent meta-analysis by Hedengran and co-workers in the British Journal of Ophthalmology (BJO).1 This study compared the efficacy and safety of benzalkonium chloride (BAK)-preserved eye drops with alternatively preserved (AP) and preservative-free (PF) eye drops. The meta-analysis was conducted on 16 studies that range from 15 days to 6 months of study duration. Change in IOP in BAK vs AP and PF groups was meta-analysed as the primary outcome. Conjunctival hyperaemia, ocular hyperaemia, total ocular adverse effects (AE), and TBUT were also meta-analysed. The authors found no evidence of significant change in IOP and conjunctival hyperaemia between BAK vs AP and PF treatment groups. The authors concluded that the main reason for detecting no clinical differences between the groups was related to the lack of long-term clinical studies on the safety of BAK vs AP and PF eye drops. We are in consensus with Kontas AG et al., comments on the deficiencies of this meta-analysis.
We do not agree to the conclusion, “BAK-containing and PF medications do not differ with respect to tolerability and therapy outcome”. We would like to direct the authors and readers to our recently published study in the journal, Clinical and Experimental Ophthalmology (CEO), which involved the randomised evaluation of the inflammatory effects of PF vs BAK and PF vs polyquad (PQ)-preserved eye drops in naïve glaucomatous patients over the period of 24 months.2 We profiled the inflammatory cytokines and analysed the ocular AE (via OSDI questionnaire) at baseline and then at 1, 3, 6, 12 and 24 months, respectively. Our results showed that the pro-inflammatory cytokines such as IL-6, IL-8, and IL-1beta were significantly increased in a time-dependent fashion in BAK group compared to PF and PQ groups. Notably, the increased levels of these cytokines significantly correlated to the OSDI in BAK group. Our results conformed with previously published in-vivo and in-vitro studies.3 4
Although our study has demonstrated that PF and PQ-preserved eye drops do not elicit ocular AE, the increased levels of IL-1beta in PQ group starting 12-month onwards indicated that PQ preserved eye drops may produce delayed ocular surface discomfort. As the main aim of our study was to compare the BAK vs PF and PQ-preserved eye drops, there is a likelihood that bimatoprost could elicit ocular hyperaemia even when used as a PF formulation. A previous study has reported that bimatoprost causes vasodilation mediated via nitric oxide synthase but not through the induction of pro-inflammatory cytokines.5
We agree to author’s views, “Longer clinical studies with standardised safety measurements and grading methods are highly advisable to fully identify any potential differences between preservation methods.” We recommend that a longitudinal study comparing the PF-bimatoprost with BAK-preserved bimatoprost should be conducted to validate the ocular responses. Additionally, to comprehensively ascertain the effect of other analogues, it is essential to study the ocular effects of PF-latanoprost vs BAK-latanoprost and PF-travoprost vs BAK-travoprost.
Imran Mohammed
Harminder S. Dua
Anthony J. King
Academic Ophthalmology, School of Medicine, The University of Nottingham, UK
References:
1. Hedengran A, Steensberg AT, Virgili G, et al. Efficacy and safety evaluation of benzalkonium chloride preserved eye-drops compared with alternatively preserved and preservative-free eye-drops in the treatment of glaucoma: a systematic review and meta-analysis. Br J Ophthalmol 2020;104(11):1512-18. doi: 10.1136/bjophthalmol-2019-315623 [published Online First: 2020/02/14]
2. Mohammed I, Kulkarni B, Faraj LA, et al. Profiling ocular surface responses to preserved and non-preserved topical glaucoma medications: A 2-year randomized evaluation study. Clin Exp Ophthalmol 2020;48(7):973-82. doi: 10.1111/ceo.13814 [published Online First: 2020/06/22]
3. Baudouin C, Denoyer A, Desbenoit N, et al. In vitro and in vivo experimental studies on trabecular meshwork degeneration induced by benzalkonium chloride (an American Ophthalmological Society thesis). Trans Am Ophthalmol Soc 2012;110:40-63. [published Online First: 2013/07/03]
4. Baudouin C, Pisella PJ, Fillacier K, et al. Ocular surface inflammatory changes induced by topical antiglaucoma drugs: human and animal studies. Ophthalmology 1999;106(3):556-63. doi: 10.1016/S0161-6420(99)90116-1 [published Online First: 1999/03/18]
5. Impagnatiello F, Bastia E, Almirante N, et al. Prostaglandin analogues and nitric oxide contribution in the treatment of ocular hypertension and glaucoma. Br J Pharmacol 2019;176(8):1079-89. doi: 10.1111/bph.14328 [published Online First: 2018/04/19]
We read with interest the study by Özsaygili et al. in which the authors report that the presence or absence of posterior vitreous detachment (PVD) purportedly had no influence on the efficacy of aflibercept intravitreal injections in patients with diabetic macular oedema (DMO). We question the validity of this conclusion since it is known that eyes with attached vitreous require more injections to manage exudative age-related macular degeneration than eyes with PVD.1 This is presumed to be due to interference with macular access by anti-vascular endothelial growth factor (anti-VEGF) by the posterior vitreous cortex. The same mechanism of action could be expected in eyes with DMO. Thus, there may be alternative explanations for the observed lack of an effect of PVD status on the response to aflibercept. We hypothesize that the findings are due to both the unreliable diagnosis of PVD by spectral domain optical coherence tomography (SD-OCT) alone, and the possible presence of vitreoschisis.
Previous studies have shown that SD-OCT is not a robust way to diagnose PVD, since the positive predictive value is only approximately 50%.2, 3 Rather, ultrasound is the recommended way to detect complete PVD (Figure 1).2 Did Özsaygili et al. perform ultrasound in their patients? If not, they would be unable to determine true PVD status, and the validity of their conclusion needs to be called into question.
Additionally, it is unclear from the study by Özsaygili et al. wheth...
We read with interest the study by Özsaygili et al. in which the authors report that the presence or absence of posterior vitreous detachment (PVD) purportedly had no influence on the efficacy of aflibercept intravitreal injections in patients with diabetic macular oedema (DMO). We question the validity of this conclusion since it is known that eyes with attached vitreous require more injections to manage exudative age-related macular degeneration than eyes with PVD.1 This is presumed to be due to interference with macular access by anti-vascular endothelial growth factor (anti-VEGF) by the posterior vitreous cortex. The same mechanism of action could be expected in eyes with DMO. Thus, there may be alternative explanations for the observed lack of an effect of PVD status on the response to aflibercept. We hypothesize that the findings are due to both the unreliable diagnosis of PVD by spectral domain optical coherence tomography (SD-OCT) alone, and the possible presence of vitreoschisis.
Previous studies have shown that SD-OCT is not a robust way to diagnose PVD, since the positive predictive value is only approximately 50%.2, 3 Rather, ultrasound is the recommended way to detect complete PVD (Figure 1).2 Did Özsaygili et al. perform ultrasound in their patients? If not, they would be unable to determine true PVD status, and the validity of their conclusion needs to be called into question.
Additionally, it is unclear from the study by Özsaygili et al. whether vitreoschisis, defined as a split within the posterior vitreous cortex (Figure 2), was observed or documented. Although SD-OCT has the ability to detect vitreoschisis4–6, “what we see depends mainly on what we look for”, as Sir John William Lubbock once wrote. If there were cases in the series assembled by Özsaygili et al. with anomalous PVD and vitreoschisis, this could be incorrectly diagnosed as PVD, and the access of aflibercept into the macula may have been hindered by the outer wall of the vitreoschisis cavity (Figure 2), giving another reason for the false impression that PVD plays no role on aflibercept response in patients with diabetic macular oedema.
In conclusion, we agree with Sir Lubbock that we see what we seek and thus invite the authors to re-examine their data with the foregoing in mind.
References:
1. Sebag J. Vitreous in age-related macular degeneration therapy - The medium is the message. Retina. 2015;35(9):1715-1718. doi:10.1097/IAE.0000000000000718.
2. Hwang ES, Kraker JA, Griffin KJ, Sebag J, Weinberg D V, Kim JE. Accuracy of Spectral-Domain OCT of the Macula for Detection of Complete Posterior Vitreous Detachment. Ophthalmol Retin. 2020;4(2):148-153. doi:10.1016/j.oret.2019.10.013.
3. Abraham JR, Ehlers JP. Posterior Vitreous Detachment: Methods for Detection. Ophthalmol Retin. 2020;4(2):119-121. doi:10.1016/j.oret.2019.12.014.
4. Sebag J. Vitreoschisis. Graefe’s Arch Clin Exp Ophthalmol. 2008;246(3):329-332. doi:10.1007/s00417-007-0743-x.
5. Gupta P, Yee KMP, Garcia P, et al. Vitreoschisis in macular diseases. Br J Ophthalmol. 2011;95(3):376-380. doi:10.1136/bjo.2009.175109.
6. Sebag J. Vitreoschisis in diabetic macular edema. Invest Ophthalmol Vis Sci. 2011;52(11):8455-8456. doi:10.1167/iovs.11-8333.
To the Editor:
We appreciate the comments by Wei Gui and J. Sebag about Ozsaygili Cemal’s article titled ‘The effect of posterior vitreous detachment on aflibercept response in diabetic macular oedema.’1 In our study, we used the video display mode to obtain more reliable results while evaluating the posterior vitreous detachment (PVD) status with spectral-domain optical coherence tomography (SD-OCT). In a recent clinical study comparing the PVD status with ocular ultrasonography (US) and SD-OCT in patients with diabetic macular oedema (DMO), it was reported that video display mode SD-OCT showed total agreement (100% in video display mode) with US.2 We used the video display mode in all patients instead of a single cross-sectional view and excluded patients with poor image quality. Since it was a retrospective study, we could not have the chance to perform US, but excluding these patients from the study in patients where any of the 2 independent retina specialists (CO, BK) disagreed on the PVD status draws attention as factors that increase the validity of our data. In addition, the International Vitreomacular Traction Study Group, including doctor J. Sebag, has classified the posterior vitreous-macular relationship based on OCT and has mostly replaced USG with OCT in our current clinical practice.3
All eyes in our study were examined for vitreoschisis and similar anomalous PVD using SD-OCT video display mode. As you mentioned, SD-OCT has the abili...
To the Editor:
We appreciate the comments by Wei Gui and J. Sebag about Ozsaygili Cemal’s article titled ‘The effect of posterior vitreous detachment on aflibercept response in diabetic macular oedema.’1 In our study, we used the video display mode to obtain more reliable results while evaluating the posterior vitreous detachment (PVD) status with spectral-domain optical coherence tomography (SD-OCT). In a recent clinical study comparing the PVD status with ocular ultrasonography (US) and SD-OCT in patients with diabetic macular oedema (DMO), it was reported that video display mode SD-OCT showed total agreement (100% in video display mode) with US.2 We used the video display mode in all patients instead of a single cross-sectional view and excluded patients with poor image quality. Since it was a retrospective study, we could not have the chance to perform US, but excluding these patients from the study in patients where any of the 2 independent retina specialists (CO, BK) disagreed on the PVD status draws attention as factors that increase the validity of our data. In addition, the International Vitreomacular Traction Study Group, including doctor J. Sebag, has classified the posterior vitreous-macular relationship based on OCT and has mostly replaced USG with OCT in our current clinical practice.3
All eyes in our study were examined for vitreoschisis and similar anomalous PVD using SD-OCT video display mode. As you mentioned, SD-OCT has the ability to detect vitreoschisis.4,5 However, we had the chance to observe that the SD-OCT video display mode can make the fine distinction between vitreoschisis and artefact more reliably than single-section images and thanks to J. Sebag's letter for the opportunity to emphasize this once again. We think that the SD-OCT video imaging mode should be kept in mind by clinicians as it provides dynamic evaluation like USG and increases the reliability of static cross-sectional images which can rarely lead to erroneous interpretations.
We have applied the same number of injections to all eyes in our study and evaluated the short-term treatment response. However, as we mentioned in our study, further studies with longer follow-up are needed regarding the effects of PVD status on injection requirement. After intravitreal injection, larger molecules may be more exposed to the molecular sieve effect of Balaz’s in the posterior vitreous cortex6, but aflibercept also may be too small to be affected by the molecular sieve effect. Not only the presence of the attached posterior vitreous cortex but also vitreous glycation and different amounts of vitreous that had glycated cross-links and hyaluronan can also affect the permeability coefficient for diffusion7 and treatment response. The answer to whether the effect of the posterior vitreous on the treatment response is more than a mechanical barrier will be elucidated by future studies. We thank Dr. Wei Gui and J. Sebag for the interest in our study and we welcome further comments, questions, and suggestions.
Cemal OZSAYGILI, Bekir KUCUK, Yener YILDIRIM
None of the authors has any financial/conflicting interests to disclose.
References
1. Özsaygili C, Küçük B, Yildirim Y. The effect of posterior vitreous detachment on aflibercept response in diabetic macular oedema [published online ahead of print, 2020 Jul 29]. Br J Ophthalmol. 2020;bjophthalmol-2020-316155. doi:10.1136/bjophthalmol-2020-316155
2. Pessoa B, Coelho J, Malheiro L, et al. Comparison of Ocular Ultrasound Versus SD-OCT for Imaging of the Posterior Vitreous Status in Patients With DME. Ophthalmic Surg Lasers Imaging Retina. 2020;51(4):S50-S53. doi:10.3928/23258160-20200401-07
3. Duker, J. S., Kaiser, P. K., Binder, S., de Smet, M. D., Gaudric, A., Reichel, E., Sadda, S. R., Sebag, J., Spaide, R. F., & Stalmans, P. (2013). The International Vitreomacular Traction Study Group classification of vitreomacular adhesion, traction, and macular hole. Ophthalmology, 120(12), 2611–2619. https://doi.org/10.1016/j.ophtha.2013.07.042
4. Gupta, P., Yee, K. M., Garcia, P., Rosen, R. B., Parikh, J., Hageman, G. S., Sadun, A. A., & Sebag, J. (2011). Vitreoschisis in macular diseases. The British journal of ophthalmology, 95(3), 376–380. https://doi.org/10.1136/bjo.2009.175109
5. Sebag J. Vitreoschisis in diabetic macular edema. Invest Ophthalmol Vis Sci. 2011;52(11):8455-8456. doi:10.1167/iovs.11-8333.
6. Balazs EA. Die Mikrostruktur und Chemie des Glaskörpers [Microstructure and chemistry of the vitreous body]. Ber Zusammenkunft Dtsch Ophthalmol Ges. 1968;68:536-572.
7. Lee O-T, Good SD, Lamy R, et al. Advanced glycation end product accumulation reduces vitreous permeability. Invest Ophthalmol Vis Sci 2015;56:2892–2897.
We were intrigued by the study by Yang et al[1] recently published in the British Journal of Ophthalmology. They conducted a detailed analysis of the fundus screening results of 5606 infants over 5 years in tertiary neonatal intensive care units (NICUs) in four medical centres in Shanghai, China. They found the detection rate of retinopathy of prematurity (ROP)to be 15.9%, and the detection rate of type 1 ROP (1.1%) was lower than that previously reported. The mean gestational age (GA) and birth weight (BW) of infants with ROP have also decreased. Therefore, they suggest modifying the criteria of Chinese ROP screening to GA <32 weeks or BW <1600 g. Application of these criteria to the studied cohort yielded a 98.4% sensitivity, with the infants requiring fundus screening reduced by 43.2%. Therefore, these criteria would reduce medical costs significantly. This is of great significance to the screening and treatment of ROP in China, which has a huge population and regional medical resource imbalances.
However, the study also had issues that need further discussion. First, the patient cohort was not a continuous population-based cohort, and the authors did not clearly state the specific criteria for screening. Therefore, the rate could be the detection rate rather than the true incidence. In addition, the development and general conditions of these patients from NICUs are significantly different from those of the general population. Therefore, although it was a r...
We were intrigued by the study by Yang et al[1] recently published in the British Journal of Ophthalmology. They conducted a detailed analysis of the fundus screening results of 5606 infants over 5 years in tertiary neonatal intensive care units (NICUs) in four medical centres in Shanghai, China. They found the detection rate of retinopathy of prematurity (ROP)to be 15.9%, and the detection rate of type 1 ROP (1.1%) was lower than that previously reported. The mean gestational age (GA) and birth weight (BW) of infants with ROP have also decreased. Therefore, they suggest modifying the criteria of Chinese ROP screening to GA <32 weeks or BW <1600 g. Application of these criteria to the studied cohort yielded a 98.4% sensitivity, with the infants requiring fundus screening reduced by 43.2%. Therefore, these criteria would reduce medical costs significantly. This is of great significance to the screening and treatment of ROP in China, which has a huge population and regional medical resource imbalances.
However, the study also had issues that need further discussion. First, the patient cohort was not a continuous population-based cohort, and the authors did not clearly state the specific criteria for screening. Therefore, the rate could be the detection rate rather than the true incidence. In addition, the development and general conditions of these patients from NICUs are significantly different from those of the general population. Therefore, although it was a relatively representative multi-centre study, these results may not fully represent the incidence in the whole region. More population-based studies on ROP screening in a wider area could supplement and enrich the data of this study, which would provide a more comprehensive and clearer assessment of the incidence of ROP in Shanghai and China.
Second, this was a retrospective study. The authors mentioned that the results could be used as a reliable basis to improve the ROP screening guideline in China, which is insufficiently rigorous. Recent reports show that more mature infants and those with a higher BW are also at risk of developing severe ROP in developing countries [2, 3]. Dou et al [4] reported 20 cases of stage 5 ROP in north-western China, among whom 2 had GA >34 weeks and 4 had BW >2000 g. A prospective study in two medical centres in Shanghai found that if their criteria (GA ≤33 weeks or BW ≤1750 g) were adopted, any infant with ROP who needed treatment would be identified, and the number of infants needing examinations could be reduced by 16.9%[5]. If further prospective observations were conducted to examine the criteria recommended in this study (GA <32 weeks or BW <1600 g) and take the current guideline as a control, it would be more convincing.
Finally, many paediatric patients are referred to Shanghai from neighbouring areas. The investigators did not specify whether the infants were first screened in their medical centres or other hospitals. Therefore, the selection bias of the study could not be evaluated, which weakened the credibility of the results. If the authors could further explain the source and regional distribution of the participants, the results would be more convincing.
Liang Wang, Zifeng Zhang, Manhong Li, Yusheng Wang
Department of Ophthalmology, Eye Institute of Chinese PLA, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, China
Correspondence to Zifeng Zhang, Department of Ophthalmology, Eye Institute of Chinese PLA, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, China; Email: zzffmmu@163.com; Yusheng Wang, Department of Ophthalmology, Eye Institute of Chinese PLA, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, China; Email: wangys003@126.com
Funding Grants from the National Natural Science Foundation of China (81770936)
References
1 Yang Q, Zhou X, Ni Y, et al. Optimised retinopathy of prematurity screening guideline in China based on a 5-year cohort study. Br J Ophthalmol, doi: 1136/bjophthalmol-2020-316401
2 Zhang Z, Li M, Wang Y, et al. Analysis of retinopathy of prematurity with birth weight higher than 2 kg in Xi'an area. Chin J Ophthalmol 2014;50:184-8.
3 Chen Y, Li X. Characteristics of severe retinopathy of prematurity patients in China: a repeat of the first epidemic? Br J Ophthalmol 2006;90:268-71.
4 Dou G, Li M, Zhang Z, et al. Demographic profile and ocular characteristics of stage 5 retinopathy of prematurity at a referral center in Northwest China: implications for implementation. BMC Ophthalmol 2018;18. doi: 10.1186/s12886-018-0975-z
5 Xu Y, Zhou X, Zhang Q, et al. Screening for retinopathy of prematurity in China: a neonatal units-based prospective study. Invest Ophthalmol Vis Sci 2013;54:8229-36
I have read with interest the paper by Fabian ID et al. “Travel burden and clinical presentation of retinoblastoma”[1]. I acknowledge the efforts conducted by the authors to build a retinoblastoma knowledge based on a large consortium for the first time. Many publications have agreed that the underprivileged socioeconomic situations affect the presentation and outcome of retinoblastoma patients[2, 3]. The measures used in most publications, including the one by Fabian ID et al., are national-level measures. Such socioeconomic measures on the country level affect the roads and travel quality beside family and healthcare giver education and training. A better measure in such cases is an individual level for each family. In developing countries, a vast gap presents between inhabitants letting a country-level measure, not representative. As mentioned in a glimpse in the paper, patients can spend a long time orbiting multiple physicians before targeting the oncology center. On the other side, people with higher economic status can get better healthcare and travel longer distances comfortably and present to centers with early stages.
Show MoreFurthermore, Figure 2 shows interestingly similar small catchment areas in Africa; this raised a question on the data that were used for drawing the figure; is it individualized for each center? Additionally, if the analysis depended on the permanent address.
Egypt’s major pediatric oncology center, which was included in the study, cover...
We thank Alfaar for their comment on our paper titled: “Travel burden and clinical presentation of retinoblastoma: analysis of 1024 patients from 43 African countries and 518 patients from 40 European contries”.[1]
Show MoreIn our paper, we compared the stage of presentation of newly diagnosed retinoblastoma patients from African and European countries and investigated possible associations to the travel distance from home to treatment centre. Our findings suggest that treatment centres in African countries serve patients that reside, on average, in closer proximity to the treatment center than in Europe (186 km average distance travelled in Africa compared to an average distance travelled of 422 km in Europe). In reply to Alfaar’s comment, to produce these numbers, we calculated the average travel distance in a country and then calculated the mean of averages in a continent and compared Africa to Europe.
The red circles in Figure 2 in our original paper,[1] representing the mean travel distance in a continent, were superimposed on each centre on a scaled map. All red circles in Africa are similar in size (i.e. radius of 186 km) and all in Europe are similar (i.e. radius of 422 km).
We agree with Alfaar that our analysis has several limitations, some of which are mentioned in our paper and some, rightfully, in his eLetter. In a study, in which patients from over 80 countries in two continents are included, one cannot take into account all considerations, especiall...
Reply to the comment on: “Influence of corneal guttae and nuclear cataract on contrast sensitivity”
We thank Sanjay V Patel for the comments. Patients with Fuchs endothelial corneal dystrophy (FECD) are known to have reduced contrast sensitivity due to corneal edema and guttae. Before the introduction of endothelial keratoplasty, penetrating keratoplasty had been performed mainly in patients with advanced FECD and clinically significant corneal edema. However, as endothelial keratoplasty procedures such as Descemet membrane endothelial keratoplasty can bring excellent visual acuity outcomes, surgery can be performed earlier and even in cases without any clinical corneal edema. Therefore, it has become even more important to detect the causes of visual impairment in patients with FECD. In our retrospective study, we enrolled FECD patients with >5 mm of confluent guttae and no corneal edema (modified Krachmer grade 5). When analyzed by Scheimpflug tomography, our FECD patients showed no difference in the central corneal thickness and corneal volume when compared to the control group of cataract patients without any corneal pathologies.1 Recently, Sun et al. presented a new method to detect subclinical corneal edema in patients with FECD.2,3 The authors analyzed three Scheimpflug tomography pachymetry map and posterior elevation map patterns to detect subclinical edema in FECD patients: loss of regular isopachs, displacement of the thinnest point of the cornea, and...
Show MoreMcCann et al. reported factors of the associations with intraocular pressure (IOP) and circumpapillary retinal nerve fibre layer (cRNFL) thickness (1). Increased IOP and reduced cRNFL were associated with increased age, myopic refractive error, male sex and hypertension. In addition, Alzheimer's disease was associated with thinner average global cRNFL, and Parkinson's disease (PD) and current smoking status were associated with thicker average global cRNFL, and I present recent information regarding their study in patients with PD.
Murueta-Goyena et al. reported the association between the changes of retinal thickness and their predictive value as biomarkers of disease progression in idiopathic PD (2). The authors used macular ganglion-inner plexiform layer complex (mGCIPL) and peripapillary retinal nerve fiber layer (pRNFL) thickness reduction rates, and the Montreal Cognitive Assessment (MoCA) questionnaire was also applied. The adjusted relative risks of lower parafoveal mGCIPL and pRNFL thickness at baseline for an increased risk of cognitive decline at 3 years significantly increased. This means that reduced retinal thickness is a risk factor of cognitive impairment in patients with PD. McCann et al. did not evaluate cRNFL in PD patients with cognitive impairment, and I suppose that progression of cognitive impairment in patients with PD might accelerate reduction of average global cRNFL.
Second, Sung et al. also investigated the association be...
Show MoreDear Editor,
Corneal graft rejection following vaccination was first reported in 1988 by T L Steinemann, B H Koffler and C D Jennings [1]. This article is missing from Table 1, “Summary of reported cases of corneal graft rejection”. As it is the first published study to describe this temporal association, it merits mention.
In regards to preventative measures, we recommend thoroughly counseling patients with grafts. They should be educated on the salient warning signs of rejection including pain, redness, blurred vision, and irritation. Patients should also be informed that COVID-19 vaccination may pose a risk to the viability of their corneal grafts. We recommend prophylactically increasing topical steroids for 3-4 weeks around the time of each vaccination.
References
1. Steinemann TL, Koffler BH, Jennings CD. Corneal allograft rejection following immunization. Am J Ophthalmol. 1988 Nov 15;106(5):575-8. doi: 10.1016/0002-9394(88)90588-0. PMID: 3056015.
Atik et al (BJOhttps://bjo.bmj.com/content/105/5/602) have done an excellent job of summarizing the current state of the art for conducting health economic evaluations in ophthalmology. Not surprisingly, however, such tools and techniques were originally designed to address broader questions of healthcare funding and resource allocation across many disparate clinical areas. As such, the general use case was very far removed from ophthalmology. This is relevant as a central component is the calculation of the utility parameters used, particularly in cost-effectiveness calculations (1). At present, the standard default utility measure remains the EQ5D, which does not prima facie include a vision specific domain (2). Rather, a “Vision Bolt-On” to the EQ5D which asks patients whether they “Have no problems seeing”; “Have some problem seeing”; or “Have extreme problems seeing” is proposed for increasing the precision of the utility score derived from patients for ophthalmic interventions (3). Unfortunately, the “Vision Bolt On” while theoretically increasing the discriminating power of the EQ-5D has not been widely adopted in economic evaluations conducted in ophthalmology (3-4). Moreover, as currently configured, the “Vision Bolt On” questions fail to adequately account for the clinical differences, say between central or fine reading vision which may be more relevant in patients with age-related macular degeneration, versus...
Show MoreDear Editor:
We welcome the recent meta-analysis by Hedengran and co-workers in the British Journal of Ophthalmology (BJO).1 This study compared the efficacy and safety of benzalkonium chloride (BAK)-preserved eye drops with alternatively preserved (AP) and preservative-free (PF) eye drops. The meta-analysis was conducted on 16 studies that range from 15 days to 6 months of study duration. Change in IOP in BAK vs AP and PF groups was meta-analysed as the primary outcome. Conjunctival hyperaemia, ocular hyperaemia, total ocular adverse effects (AE), and TBUT were also meta-analysed. The authors found no evidence of significant change in IOP and conjunctival hyperaemia between BAK vs AP and PF treatment groups. The authors concluded that the main reason for detecting no clinical differences between the groups was related to the lack of long-term clinical studies on the safety of BAK vs AP and PF eye drops. We are in consensus with Kontas AG et al., comments on the deficiencies of this meta-analysis.
We do not agree to the conclusion, “BAK-containing and PF medications do not differ with respect to tolerability and therapy outcome”. We would like to direct the authors and readers to our recently published study in the journal, Clinical and Experimental Ophthalmology (CEO), which involved the randomised evaluation of the inflammatory effects of PF vs BAK and PF vs polyquad (PQ)-preserved eye drops in naïve glaucomatous patients over the period of 24 months.2 We p...
Show MoreWe read with interest the study by Özsaygili et al. in which the authors report that the presence or absence of posterior vitreous detachment (PVD) purportedly had no influence on the efficacy of aflibercept intravitreal injections in patients with diabetic macular oedema (DMO). We question the validity of this conclusion since it is known that eyes with attached vitreous require more injections to manage exudative age-related macular degeneration than eyes with PVD.1 This is presumed to be due to interference with macular access by anti-vascular endothelial growth factor (anti-VEGF) by the posterior vitreous cortex. The same mechanism of action could be expected in eyes with DMO. Thus, there may be alternative explanations for the observed lack of an effect of PVD status on the response to aflibercept. We hypothesize that the findings are due to both the unreliable diagnosis of PVD by spectral domain optical coherence tomography (SD-OCT) alone, and the possible presence of vitreoschisis.
Previous studies have shown that SD-OCT is not a robust way to diagnose PVD, since the positive predictive value is only approximately 50%.2, 3 Rather, ultrasound is the recommended way to detect complete PVD (Figure 1).2 Did Özsaygili et al. perform ultrasound in their patients? If not, they would be unable to determine true PVD status, and the validity of their conclusion needs to be called into question.
Additionally, it is unclear from the study by Özsaygili et al. wheth...
Show MoreReply
To the Editor:
Show MoreWe appreciate the comments by Wei Gui and J. Sebag about Ozsaygili Cemal’s article titled ‘The effect of posterior vitreous detachment on aflibercept response in diabetic macular oedema.’1 In our study, we used the video display mode to obtain more reliable results while evaluating the posterior vitreous detachment (PVD) status with spectral-domain optical coherence tomography (SD-OCT). In a recent clinical study comparing the PVD status with ocular ultrasonography (US) and SD-OCT in patients with diabetic macular oedema (DMO), it was reported that video display mode SD-OCT showed total agreement (100% in video display mode) with US.2 We used the video display mode in all patients instead of a single cross-sectional view and excluded patients with poor image quality. Since it was a retrospective study, we could not have the chance to perform US, but excluding these patients from the study in patients where any of the 2 independent retina specialists (CO, BK) disagreed on the PVD status draws attention as factors that increase the validity of our data. In addition, the International Vitreomacular Traction Study Group, including doctor J. Sebag, has classified the posterior vitreous-macular relationship based on OCT and has mostly replaced USG with OCT in our current clinical practice.3
All eyes in our study were examined for vitreoschisis and similar anomalous PVD using SD-OCT video display mode. As you mentioned, SD-OCT has the abili...
We were intrigued by the study by Yang et al[1] recently published in the British Journal of Ophthalmology. They conducted a detailed analysis of the fundus screening results of 5606 infants over 5 years in tertiary neonatal intensive care units (NICUs) in four medical centres in Shanghai, China. They found the detection rate of retinopathy of prematurity (ROP)to be 15.9%, and the detection rate of type 1 ROP (1.1%) was lower than that previously reported. The mean gestational age (GA) and birth weight (BW) of infants with ROP have also decreased. Therefore, they suggest modifying the criteria of Chinese ROP screening to GA <32 weeks or BW <1600 g. Application of these criteria to the studied cohort yielded a 98.4% sensitivity, with the infants requiring fundus screening reduced by 43.2%. Therefore, these criteria would reduce medical costs significantly. This is of great significance to the screening and treatment of ROP in China, which has a huge population and regional medical resource imbalances.
Show MoreHowever, the study also had issues that need further discussion. First, the patient cohort was not a continuous population-based cohort, and the authors did not clearly state the specific criteria for screening. Therefore, the rate could be the detection rate rather than the true incidence. In addition, the development and general conditions of these patients from NICUs are significantly different from those of the general population. Therefore, although it was a r...
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