We thank Drs Sabherwal and Sood for their interest in our article.(1) We would like to respond to the interesting points they raise.
Table 3 presents our analyses of potential predictors of the correct diagnosis by rural doctors of diabetic retinopathy (DR) requiring treatment. Details on a number of the characteristics assessed in this table are presented in the first paragraph of the Results section, but not, as Drs Sabherwal and Sood point out, the proportion having received didactic training. Among the 28 rural doctors, 13 (46.4%) received such training and 15 (53.6%) did not.
In the Methods, we describe in detail the training received by ophthalmologists in the CREST (Comprehensive Rural Eye Service and Training) program. As described there, only two doctors per hospital (not all of whom examined patients in the current study) could attend the didactic phase of training at the Zhongshan Ophthalmic Center (ZOC). This is due to the limited number of ophthalmologists at a typical rural Chinese county hospital, and the heavy load of clinical duties. For more doctors to have left their facilities for the two-month didactic training would not have been practical. However, all ophthalmologists participating in the CREST network and in the current study received intensive hands-on training by medical retina experts from ZOC at their own facilities, which included the diagnosis and laser treatment of diabetic retinopathy (DR) as well as the u...
We thank Drs Sabherwal and Sood for their interest in our article.(1) We would like to respond to the interesting points they raise.
Table 3 presents our analyses of potential predictors of the correct diagnosis by rural doctors of diabetic retinopathy (DR) requiring treatment. Details on a number of the characteristics assessed in this table are presented in the first paragraph of the Results section, but not, as Drs Sabherwal and Sood point out, the proportion having received didactic training. Among the 28 rural doctors, 13 (46.4%) received such training and 15 (53.6%) did not.
In the Methods, we describe in detail the training received by ophthalmologists in the CREST (Comprehensive Rural Eye Service and Training) program. As described there, only two doctors per hospital (not all of whom examined patients in the current study) could attend the didactic phase of training at the Zhongshan Ophthalmic Center (ZOC). This is due to the limited number of ophthalmologists at a typical rural Chinese county hospital, and the heavy load of clinical duties. For more doctors to have left their facilities for the two-month didactic training would not have been practical. However, all ophthalmologists participating in the CREST network and in the current study received intensive hands-on training by medical retina experts from ZOC at their own facilities, which included the diagnosis and laser treatment of diabetic retinopathy (DR) as well as the use of the United Kingdom National Health Service Diabetic Eye Screening Program (UK NHS DESP) DR grading system assessed in our study. The median number (inter-quartile range) of hands-on training sessions received in managing DR was 3 (1, 9). As mentioned in our article, CREST is a fully-funded program by Orbis International. It provides DR training well beyond what the typical rural county-level ophthalmologist in China would receive. Training in the UK NHS DESP system was comparable between non-medical graders and doctors. For these reasons, the authors would respectfully disagree with Drs Sabherwal and Sood’s suggestion that our study was biased in favour of non-medical graders. These graders achieved a level of accuracy consistent with the standards of the UK NHS DESP, and the use of non-medical graders has been recommended by bodies such as the UK Royal College of Ophthalmologists.(2)
Drs Sabherwal and Sood also indicate that our use of an arbiter may have improved the accuracy of non-medical graders and added to the expense of the program. Use of an arbiter is standard practice in the UK NHS DESP, whose protocols we follow in CREST, and in most DR screening programs of which we are aware. As noted in our article, performance of graders on those images where the grade was unchanged by arbitration remained good: the median sensitivity was 0.80, specificity was 0.98 and kappa ranged from 0.78-0.88. Use of arbitration is an inherent cost of most such programs, and will be included in our forthcoming paper on cost-effectiveness for DR screening of non-medical graders versus local ophthalmologists. It should be noted that task-shifting approaches such as the use of non-medical graders, by reducing even when they do not eliminate the role of more expensive ophthalmologists, are very likely to be more cost-effective than traditional ophthalmologist-driven approaches.
Finally, Drs Sabherwal and Sood point out 33% of images being deemed of inadequate quality as a short-coming of our program. As clearly described in the Results section of our paper, the majority of such images were “inadequate” only in the sense that a single image, rather than two as required under UK NHS DESP protocols, had been made of the eye. In fact, as we reported, the proportion of eyes to which non-medical graders were unable to assign DR grades was 3.28% (24/732).
The authors would again like to thank Drs Sabherwal and Sood for their interest in our work, and the Editors for the opportunity to clarify the interesting and important issues they have raised.
1. Sabherwal S, Sood I. Comments on: "Accuracy of trained rural ophthalmologists versus non-medical image graders in the diagnosis of diabetic retinopathy in rural China". Br J Ophthalmol 2018. https://bjo.bmj.com/content/102/11/1471.responses
We read the article ‘Acute retinal toxicity associated with a mixture of perfluorooctane and perfluorohexyloctane: Failure of another indirect cytotoxicity analysis ’ by Coco et al. with great interest.[1] In this study, the authors reported on ocular toxicity due to perfluorooctane (PFO). They advised that the protocols used to determine the cytotoxicity of intraocular medical devices (which have been approved by the Organisation for the Standardisation of International Standards based on indirect methods) should be revised to ensure safety. We congratulate Coco et al.1 for their report because we believe that it has the potential to be a significant contribut or to the literature on this topic.
As is commonly known, PFO is saturated with PFO liquids, which have highly stable carbon-fluorine bonds that consequently make them inert. PFO has highly specific gravity, low viscosity, optical clarity immiscibility in water and interface tension towards water. It is regularly used in vitreoretinal surgery for complex retinal detachment repair because it displaces subretinal fluid and blood anteriorly, unfolds the retina in giant retinal tear cases and provides counter traction and retinal stabilisation during membrane peeling in eyes with proliferative vitreoretinopathy.[2,3] These properties make PFO useful for intraocular surgery. However, some limitations exist regarding PFO use as a long- term tamponade such as amaurosis, a lack of light perce...
We read the article ‘Acute retinal toxicity associated with a mixture of perfluorooctane and perfluorohexyloctane: Failure of another indirect cytotoxicity analysis ’ by Coco et al. with great interest.[1] In this study, the authors reported on ocular toxicity due to perfluorooctane (PFO). They advised that the protocols used to determine the cytotoxicity of intraocular medical devices (which have been approved by the Organisation for the Standardisation of International Standards based on indirect methods) should be revised to ensure safety. We congratulate Coco et al.1 for their report because we believe that it has the potential to be a significant contribut or to the literature on this topic.
As is commonly known, PFO is saturated with PFO liquids, which have highly stable carbon-fluorine bonds that consequently make them inert. PFO has highly specific gravity, low viscosity, optical clarity immiscibility in water and interface tension towards water. It is regularly used in vitreoretinal surgery for complex retinal detachment repair because it displaces subretinal fluid and blood anteriorly, unfolds the retina in giant retinal tear cases and provides counter traction and retinal stabilisation during membrane peeling in eyes with proliferative vitreoretinopathy.[2,3] These properties make PFO useful for intraocular surgery. However, some limitations exist regarding PFO use as a long- term tamponade such as amaurosis, a lack of light perception, optic nerve atrophy, acute retinal necrosis and retinal vascular occlusion (both arterial and/or venous) with disseminated haemorrhages.
Notably, there are controversial results regarding PFO toxicity in the literature. [3-9] The present study was one of the few reports to discuss ocular toxicity due to PFO in the last few years.
Using the current study by Coco et al.1 as a foundation, we would like to share our findings regarding the ocular toxicity of PFO. In our clinic, four patients underwent uneventful vitreoretinal surgery with PFO on the same day by two experienced surgeons (BB, SG). Each patient presented with vitritis, hypopyon and acute retinal toxicity, with no increases seen in either postoperative increased intraocular pressure or pain. Figure 1 (https://i.hizliresim.com/6NQWR0.jpg) shows macular atrophy due to PFO toxicity.
Ocular toxicity may be either mechanical or chemical due to inhibition of and/or changes to tissue functionality and/or rearrangement of tissue parts and inflammatory reactions and/or immune reactions that result in function loss. In the past, intraocular injections of aminoglycoside caused occlusive vascular changes, which were attributed to the pH of the antibiotic.[10] The mechanism of PFO ocular toxicity may be similar. In addition, concentration and contact time may lead to toxicity. For instance, in 2013, some cases of acute blindness due to PFO were reported by Chile’s Health Authorities, while four cases were reported in Spain to the Agency of Medicines and Medical Devices. The problems were attributed to careless manipulation of the Turkish product ; variable concentrations of perfluorodecalin were found in the octane, after which the product was withdrawn.
Unfortunately, scientific reports have yet to clarify the causes of acute blindness. These results may help clinicians choose a short-term ocular tamponade when performing a vitrectomy. In addition, when faced with severe early postoperative intraocular inflammation, such as either vitritis or hypopyon, they should use PFO with care due to the possibility of toxicity and consider early systemic steroid treatment.
In conclusion, more chemical research is needed to clarify the acute ocular toxicity of PFO to ensure the safety of human patients. Additionally, immediate updates to both the European and Organisation for the Standardisation of International Standards guidelines for the biological evaluation of ophthalmic devices are needed.
REFERENCES
1. Coco RM, Srivastava GK, Andrés-Iglesias C, et al. Acute retinal toxicity associated with a mixture of perfluorooctane and perfluorohexyloctane: Failure of another indirect cytotoxicity analysis British Journal of Ophthalmology Published Online First: 29 March 2018. doi: 10.1136/bjophthalmol-2017-311471.
2. Loewenstein A, Humayun MS, de Juan E Jr, et al. Perfluoroperhydrophenanthrene versus perfluoro-n-octane in vitreoretinal surgery. Ophthalmology. 2000;107:1078–1082.
3. Abboud EB, Al-Falah M. Nine Years of Retained Perfluoro-n-octane in the Anterior Chamber after Retinal Detachment Repair with No Signs of Ocular Toxicity. Middle East African Journal of Ophthalmology. 2014;21(3):279-282. doi:10.4103/0974-9233.134697.
4. Stefano Zenoni, Mario R Romano, Sonia Palmieri, Natalia Comi, Edoardo Fiorentini, Piero Fontana. Ocular tolerance and efficacy of short-term tamponade with double filling of polydimethyloxane and perfluoro-n-octane. Clinical Ophthalmology 2011:5 443–449.
5. Zeana D, Becker J, Kuckelkorn R, Kirchhof B. Perfluorohexyloctane as a long-term vitreous tamponade in the experimental animal. Experimental perfluorohexyloctane substitution. Int Ophthalmol. 1999;23(1):17-24.
6. Chang S, Sparrow JR, Iwamoto T, Gershbein A, Ross R, Ortiz R. Experimental studies of tolerance to intravitreal perfluoro-n-octane liquid. Retina. 1991;11(4):367-74. PMID: 1813951.
7. Alharbi SS, Asiri MS. Reversible Corneal Toxicity of Retained Intracameral Perfluoro-n-octane. Middle East African Journal of Ophthalmology. 2016;23(3):277-279. doi:10.4103/0974-9233.186160.
8. Pastor JC, Coco RM, Fernandez-Bueno I, Alonso-Alonso ML, Medina J, Sanz-Arranz A, Rull F, Gayoso MJ, Dueñas A, Garcia-Gutierrez MT, Gonzalez-Buendia L, Delgado-Tirado S, Abecia E, Ruiz-Miguel M, Serrano MA, Ruiz-Moreno JM, Srivastava GK. Acute retinal damage after using a toxic perfuoro-octane for vitreo-retinal surgery. Retina. 2017 Jun;37(6):1140-1151. doi: 10.1097/IAE.0000000000001680.
9. Pradeep S, Chhablani JK, Patel B, Rani P. Delayed inflammation associated with retained perfluorocarbon liquid. Indian J Ophthalmol. 2011 Sep-Oct;59(5):396-8. doi: 10.4103/0301-4738.83623. PMID: 21836352.
10. Waltz K, Margo CE. Intraocular gentamicin toxicity. Arch Ophthalmol 1991;109:911.
Figure Legends:
Figure 1: A 34-year-old man with a macula on a bullous retinal detachment of his right eye. His preoperative visual acuity was 16/20. He was operated on with a 23-G pars plana vitrectomy plus SF6 and a laser. One week after surgery, he complained of very low visual acuity, and he had vitritis, hypopyon and acute retinal toxicity. The patient treated with intravenous methylprednisolone ( 1 mg/kg) and topical prednisolone, moxifloxacin, nepafenac eyedrops four times a day during 4 weeks. One month after surgery, profound atrophy of all layers of the retina were seen on optical coherence tomography. His final visual acuity was counting fingers.
We read with interest the masterly review of the neuro-ophthalmology of Behcet’s disease by Alghamdi et al (1). One small aspect we question. The authors state that in their patients with papilledema: “The diagnosis of CVT was documented in all patients by cerebral angiography and MRI showing partial or total lack of filling of at least one dural sinus and an elevated CSF opening pressure (>25 mm Hg) on lumbar puncture.” We have recently reported 8 BD patients with pseudotumor cerebri who did not have cerebral venous thrombosis (CVT) on MRI or MRV (2). Partial or total lack of filling of one venous sinus does not constitute the pathophysiological basis for intracranial hypertension; either the sagittal sinus must be occluded, or if only one transverse sinus is occluded then the other needs to be stenosed (3). It would be interesting to know what a review of their patient’s images by a neuro-radiologist would reveal.
1: Alghamdi A, Bodaghi B, Comarmond C, Desbois AC, Domont F, Wechsler B, Depaz R, Le Hoang P, Cacoub P, Touitou V, Saadoun D. Neuro-ophthalmological manifestations of Behçet's disease. Br J Ophthalmol. 2018 Apr 26. pii: bjophthalmol-2017-311334. doi: 10.1136/bjophthalmol-2017-311334.
2: Akdal G, Yaman A, Men S, Çelebisoy N, Toydemir HE, Bajin MS, Akman-Demir G. Pseudotumor cerebri syndrome without cerebral venous sinus thrombosis in Behçet's disease. J Neurol Sci. 2017;383:99-100.
3: Halmagyi GM, Ahmed RM, Johnston IH. The Pseudo...
We read with interest the masterly review of the neuro-ophthalmology of Behcet’s disease by Alghamdi et al (1). One small aspect we question. The authors state that in their patients with papilledema: “The diagnosis of CVT was documented in all patients by cerebral angiography and MRI showing partial or total lack of filling of at least one dural sinus and an elevated CSF opening pressure (>25 mm Hg) on lumbar puncture.” We have recently reported 8 BD patients with pseudotumor cerebri who did not have cerebral venous thrombosis (CVT) on MRI or MRV (2). Partial or total lack of filling of one venous sinus does not constitute the pathophysiological basis for intracranial hypertension; either the sagittal sinus must be occluded, or if only one transverse sinus is occluded then the other needs to be stenosed (3). It would be interesting to know what a review of their patient’s images by a neuro-radiologist would reveal.
1: Alghamdi A, Bodaghi B, Comarmond C, Desbois AC, Domont F, Wechsler B, Depaz R, Le Hoang P, Cacoub P, Touitou V, Saadoun D. Neuro-ophthalmological manifestations of Behçet's disease. Br J Ophthalmol. 2018 Apr 26. pii: bjophthalmol-2017-311334. doi: 10.1136/bjophthalmol-2017-311334.
2: Akdal G, Yaman A, Men S, Çelebisoy N, Toydemir HE, Bajin MS, Akman-Demir G. Pseudotumor cerebri syndrome without cerebral venous sinus thrombosis in Behçet's disease. J Neurol Sci. 2017;383:99-100.
3: Halmagyi GM, Ahmed RM, Johnston IH. The Pseudotumor Cerebri Syndrome: A Unifying Pathophysiological Concept for Patients with Isolated Intracranial Hypertension with Neither Mass Lesion Nor Ventriculomegaly. Neuroophthalmology. 2014;38:249-253.
We have read with great interest the e-letter from Karakucuk et al. published in BJO responding to our paper titled ‘Acute retinal toxicity associated with a mixture of perfluorooctane and perfluorohexyloctane: Failure of another indirect cytotoxicity analysis ’ and we appreciate their positive appreciation of our research work.
We consider extraordinarily important that they have reported four more cases in their country, thus, supporting that acute toxicity cases were not a Spanish problem as has been stated by some retinologist at an European congress (Barcelona, September 2017).
We believe that this letter should encourage other colleagues from other countries from all over the world to report cases that certainly exist, according to non-official information from several companies.
We completely agree that the ISO (the International Organization for Standardization) guidelines to determine the in vitro cytotoxicity of intraocular medical devices should be immediately changed. These guidelines should adopt direct cytotoxicity methods to be performed with finished, sterilized, and ready for release products. The analytical method utilized should include cells or tissues close to those of the retina to guarantee specific sensitivity and should be scientifically validated.
We support the suggestion of increasing chemical research, because some companies are promoting chemical tests, as a “safety guarantee”, whose scientific validity and their direct...
We have read with great interest the e-letter from Karakucuk et al. published in BJO responding to our paper titled ‘Acute retinal toxicity associated with a mixture of perfluorooctane and perfluorohexyloctane: Failure of another indirect cytotoxicity analysis ’ and we appreciate their positive appreciation of our research work.
We consider extraordinarily important that they have reported four more cases in their country, thus, supporting that acute toxicity cases were not a Spanish problem as has been stated by some retinologist at an European congress (Barcelona, September 2017).
We believe that this letter should encourage other colleagues from other countries from all over the world to report cases that certainly exist, according to non-official information from several companies.
We completely agree that the ISO (the International Organization for Standardization) guidelines to determine the in vitro cytotoxicity of intraocular medical devices should be immediately changed. These guidelines should adopt direct cytotoxicity methods to be performed with finished, sterilized, and ready for release products. The analytical method utilized should include cells or tissues close to those of the retina to guarantee specific sensitivity and should be scientifically validated.
We support the suggestion of increasing chemical research, because some companies are promoting chemical tests, as a “safety guarantee”, whose scientific validity and their direct correlation with biological tests has not yet been established. As you mentioned the presence of variable concentrations of non-fully fluorinate compounds are undesirable, but these compounds have not been related to acute toxic pictures such as those mentioned in our paper, and probably in your patients, although they could be the bases of variable intraocular inflammatory responses, that prevent the use of PFO as a long-term endotamponade agent.
It has come to our attention that three of the patients (# 2 and #3, half-brothers, and #10) from our paper in BJO (1) have been reported previously with video recordings but without eye movement recordings at age 0 to 3 years in symposium proceedings (1) prior to the eye movement recordings made at age 6-11 presented in this study.
Yours sincerely
Irene Gottlob
References
1) Pieh C, Simonsz-Toth B, Gottlob I. Nystagmus characteristics in congenital stationary night blindness (CSNB). Br J Ophthalmol 2008;92:236-240.
2) Simonsz HJ, Gottlob I, Kommerell G, Hergersberg M, Eriksson AW: Transient Infantile Upgaze Holding Insufficiency: Frühsymptom bei inkompl. cong. stat. Nachtblindheit und periventrikulärer Leukomalazie. Der Ophthalmologe 1998;95(suppl 1/1):178.
We read the article published by McKenna, et al (1) with great interest and laud them on the quality and design of their study. Screening for diabetic retinopathy in rural, low resource settings is the need of the hour, however models which are cost effective, yet provide intensive screening and continuum of care are limited. Keeping this in mind, we feel that there are a few points requiring further clarity in this article.
The odds-ratio calculated in table 3 displays the significant effect of didactic training on correct diagnosis by rural doctors. However, for the odds-ratio to be calculated, there would have been a comparison group of rural doctors who were not provided didactic training. The numbers of these doctors have not been mentioned, and no details have been provided as to whether they were given any basic level of training related to the program. In the results provided for comparison between rural doctors and the non-medical graders, it has not been made clear whether doctors who had not been provided didactic training were included. In that case, results presented in the study may have been biased towards the non-medical graders.
In the study, the arbitrator changed the grade for a high percentage of the cases, moreover, 33% of the images were not found to be of adequate quality. Hiring an arbitrator, re-checking the grading and assuring high quality images (2) through standard equipment and trained personnel would drive up...
We read the article published by McKenna, et al (1) with great interest and laud them on the quality and design of their study. Screening for diabetic retinopathy in rural, low resource settings is the need of the hour, however models which are cost effective, yet provide intensive screening and continuum of care are limited. Keeping this in mind, we feel that there are a few points requiring further clarity in this article.
The odds-ratio calculated in table 3 displays the significant effect of didactic training on correct diagnosis by rural doctors. However, for the odds-ratio to be calculated, there would have been a comparison group of rural doctors who were not provided didactic training. The numbers of these doctors have not been mentioned, and no details have been provided as to whether they were given any basic level of training related to the program. In the results provided for comparison between rural doctors and the non-medical graders, it has not been made clear whether doctors who had not been provided didactic training were included. In that case, results presented in the study may have been biased towards the non-medical graders.
In the study, the arbitrator changed the grade for a high percentage of the cases, moreover, 33% of the images were not found to be of adequate quality. Hiring an arbitrator, re-checking the grading and assuring high quality images (2) through standard equipment and trained personnel would drive up the cost of the programme. The telemedicine model by itself has already been proved as cost effective for diabetic retinopathy screening. (3) Thus, as mentioned by the authors, calculation of cost-effectiveness of the model mentioned in the study, should be carried out assessing its’ scalability.
We appreciate the opportunity to be able to discuss our views on the subject and the article in question.
References
1. McKenna M, Chen T, McAneney H, et al. Br J Ophthalmol 2018;102:1471–1476.
2. Taylor DJ, et al. Image-quality standardization for diabetic retinopathy screening. Expert Rev Ophthalmol. 2009;4(5):469–76.
3. Sharafeldin N, Kawaguchi A, Sundaram A, et al. Br J Ophthalmol 2018;102:1485–1491.
Dear Editor
We read the above paper with much interest and welcome the review and analysis of trends in acanthamoeba keratitis – a very important complication from contact lens wear. The paper discusses the incidence of acanthamoeba keratitis at Moorfields Eye Hospital, a large tertiary referral centre.
We note an incidence of 18.5 cases per annum in 1997-1999, rising to a mean of 50.3 per annum in 2011-2016 and hence has been quite rightly quoted as almost a 3 fold increase in cases.
We would however suggest some caution when using those figures to state that there is an epidemic at present.
When one attempts to take into account the fluctuations in numbers of contact lens wearers with the United Kingdom per year and relate that to incidence of acanthamoeba keratitis one has a slightly modified view.1 There has been a steady increase in contact lens wear with figures from the ACLM estimating 4.2 million CL wearers in 2016. A figure has been created showing this relative incidence in a chart format.2
The figure represents the number of cases diagnosed at Moorfields divided by the number of contact lens users (rising from 1.6 million in 1992 to 4.2 million in 2016). Therefore the mean number of cases when adjusted for CL wearers is 8.5 per year with a standard deviation of 5.8, with 11.8 in 2015 and 14 in 2016.
Whilst there is still a significant rise in cases, compared to the mainly stable period of 1996-2010, the rates are still lower t...
Dear Editor
We read the above paper with much interest and welcome the review and analysis of trends in acanthamoeba keratitis – a very important complication from contact lens wear. The paper discusses the incidence of acanthamoeba keratitis at Moorfields Eye Hospital, a large tertiary referral centre.
We note an incidence of 18.5 cases per annum in 1997-1999, rising to a mean of 50.3 per annum in 2011-2016 and hence has been quite rightly quoted as almost a 3 fold increase in cases.
We would however suggest some caution when using those figures to state that there is an epidemic at present.
When one attempts to take into account the fluctuations in numbers of contact lens wearers with the United Kingdom per year and relate that to incidence of acanthamoeba keratitis one has a slightly modified view.1 There has been a steady increase in contact lens wear with figures from the ACLM estimating 4.2 million CL wearers in 2016. A figure has been created showing this relative incidence in a chart format.2
The figure represents the number of cases diagnosed at Moorfields divided by the number of contact lens users (rising from 1.6 million in 1992 to 4.2 million in 2016). Therefore the mean number of cases when adjusted for CL wearers is 8.5 per year with a standard deviation of 5.8, with 11.8 in 2015 and 14 in 2016.
Whilst there is still a significant rise in cases, compared to the mainly stable period of 1996-2010, the rates are still lower than those experienced in 1993-4 once numbers of wearers is taken into account.
In addition, one should consider other causes for increased numbers of cases diagnosed.
Firstly one should acknowledge the increased awareness by optometrists and ophthalmologists as to the possibility of acanthamoeba keratitis and improvements in the early diagnosis.
There are also possible changes in referral patterns to Moorfields Eye Hospital from other hospitals (i.e. a high index of suspicion may lead to early transfer of suspected cases). This is certainly what we have seen in the Midlands.
The results from treatment can also be relatively good with prompt modern treatment. In a recent review of 13 confirmed cases at UHCW, Coventry over the last 12 months, none of the patients required surgical intervention and all recovered vision (with over 85% complete improvement in acuity). 45% of patients were correctly diagnosed with acanthamoeba keratitis on the first eye casualty visit and treatment was dual topical therapy.
Whilst we applaud the sentiment in this paper and the recommendations made, perhaps one needs to consider that is what was seen in one location, all be it a very large hospital – the hospitals of the 2 senior authors have seen more than 20 cases in the last year alone and hence the presentation of about 50 cases per annum cannot be easily extrapolated without taking into account a number of other factors.
1The Association for Contact Lens Manufacturers. www.aclm.org.uk. Technical summary. Contact lens year book 2016.
2Separate figure comparing CL wearers to acanthamoeba numbers from figures given by Carnt et al.
I commend the authors on an excellent study looking into the stratification of impact of macular degeneration on vision-specific function in patients with early stage AMD vs. late stage AMD. I would like to report similar findings in a United States based population with data gathered from the National Health and and Nutrition Examination Survey 2007-2008 (NHANES) which is a population based cross-sectional survey that represents the non-institutionalized population of the United States.
As the author's of this study looked at the impact of early and late ARM on vision specific functioning, I assessed a similar question using the NHANES database, specifically looking at whether patients with early and late AMD reported insufficient correction with their currently prescribed glasses or contact lenses, another measure of vision-specific functioning. After survey weighting, the sample represented a US Population of 108,719,628 people with 3.2% of participants (N=3,992) self-reporting a diagnosis of age-related macular degeneration. This represented a weighted sample of 3,479, 028 people. Of these participants reporting a diagnosis of AMD, they had a higher odds of reporting trouble seeing even with correction with glasses or contacts (OR 2.98, Confidence Interval 1.87-4.6). This relationship was held valid when controlling for age, gender, diabetes, race, self reported glaucoma, self reported cataract surgery, retinal exam evidence of retinopathy, and smoking of...
I commend the authors on an excellent study looking into the stratification of impact of macular degeneration on vision-specific function in patients with early stage AMD vs. late stage AMD. I would like to report similar findings in a United States based population with data gathered from the National Health and and Nutrition Examination Survey 2007-2008 (NHANES) which is a population based cross-sectional survey that represents the non-institutionalized population of the United States.
As the author's of this study looked at the impact of early and late ARM on vision specific functioning, I assessed a similar question using the NHANES database, specifically looking at whether patients with early and late AMD reported insufficient correction with their currently prescribed glasses or contact lenses, another measure of vision-specific functioning. After survey weighting, the sample represented a US Population of 108,719,628 people with 3.2% of participants (N=3,992) self-reporting a diagnosis of age-related macular degeneration. This represented a weighted sample of 3,479, 028 people. Of these participants reporting a diagnosis of AMD, they had a higher odds of reporting trouble seeing even with correction with glasses or contacts (OR 2.98, Confidence Interval 1.87-4.6). This relationship was held valid when controlling for age, gender, diabetes, race, self reported glaucoma, self reported cataract surgery, retinal exam evidence of retinopathy, and smoking of at least 100 cigarettes in their lifetime. This finding and the finding of the authors was further confirmed with the NHANES data showing that patients who self-reported trouble seeing with correction did not have increased odds of showing signs of early AMD on examination (OR 1.08, Confidence Interval 0.638-1.829) but had increased odds of showing signs of late AMD on examination (OR 5.16, Confidence Interval 2.97 - 8.97). Additional analysis into vision-specific function in relation to quality of life showed that these late AMD patients who reported trouble seeing even with correction had higher odds of reporting that they worried about their eyesight on a daily basis (OR 2.06, Confidence Interval 1.86-2.29).
These findings using the NHANES database confirm the findings of the authors, whom looked at a Singaporean based population and strengthen the importance of preventive public health strategies in the United States to prevent progression of early AMD to late AMD to avoid deterioration in visual acuity and quality of life.
We read the excellent paper ‘Review of extraocular muscle biopsies and utility of biopsy in extraocular muscle enlargement’ by Eade et al.1 with great interest. The authors reviewed the pathology in extraocular muscle biopsies performed over a 25-year period and reported the clinical and radiological features that might distinguish between benign and malignant diseases. As the authors note, it is imperative for the orbital surgeon to consider a muscle biopsy when the diagnosis is in doubt. With this in mind we would like to highlight two relevant cases of simulated extraocular muscle enlargement seen radiologically due to deviated ocular position rather than a pathological process related to the muscle itself. In both cases this confused the clinical picture and nearly resulted in needless surgery.
In case 1, a 42-year-old woman was referred to the oculoplastic clinic with diplopia, reduced vision in the right eye associated with retro-bulbar pain and facial paraesthesia. On examination, there was evidence of a right esotropia with a reduction of abduction (consistent with a 6th cranial nerve palsy) associated with reduced sensation involving the V1 and V2 distribution. Optic nerve function was normal. Investigations revealed an elevated serum IgG subclass 4 (1.18 g/L) and normal serum ACE. The MRI report confirmed increased girth of the right medial rectus muscle in conjunction with enlargement and pathological enhancement of right cavernous sinus extending into...
We read the excellent paper ‘Review of extraocular muscle biopsies and utility of biopsy in extraocular muscle enlargement’ by Eade et al.1 with great interest. The authors reviewed the pathology in extraocular muscle biopsies performed over a 25-year period and reported the clinical and radiological features that might distinguish between benign and malignant diseases. As the authors note, it is imperative for the orbital surgeon to consider a muscle biopsy when the diagnosis is in doubt. With this in mind we would like to highlight two relevant cases of simulated extraocular muscle enlargement seen radiologically due to deviated ocular position rather than a pathological process related to the muscle itself. In both cases this confused the clinical picture and nearly resulted in needless surgery.
In case 1, a 42-year-old woman was referred to the oculoplastic clinic with diplopia, reduced vision in the right eye associated with retro-bulbar pain and facial paraesthesia. On examination, there was evidence of a right esotropia with a reduction of abduction (consistent with a 6th cranial nerve palsy) associated with reduced sensation involving the V1 and V2 distribution. Optic nerve function was normal. Investigations revealed an elevated serum IgG subclass 4 (1.18 g/L) and normal serum ACE. The MRI report confirmed increased girth of the right medial rectus muscle in conjunction with enlargement and pathological enhancement of right cavernous sinus extending into the superior ophthalmic fissure. The patient was considered for orbital biopsy of the enlarged medial rectus muscle to ascertain the diagnosis and specifically to consider IgG4 related-disease. The MRI scan was subsequently reviewed in the regional skull-base multidisciplinary team meeting. At this stage the extraocular muscle findings were re-interpreted as being due to unopposed medial rectus contraction (i.e. the eye was in adduction at the time of the scan) secondary to a 6th cranial nerve palsy rather than pathological enlargement. This was supported by the lack of confluence between the two pathologies with sparing of the tendinous ring. The proposed orbital biopsy was therefore cancelled. Staging imaging of the chest confirmed asymmetric left hilar and borderline mediastinal lymphadenopathy which was confirmed as non-caseating granulomatous change on biopsy. A diagnosis of systemic sarcoidosis was confirmed, with cavernous sinus involvement, and the patient was successfully treated with oral prednisolone with resolution of the 6th nerve palsy.
In case 2, orbital imaging (CT) demonstrated enlargement of the inferior and horizontal recti as well as superior oblique bilaterally. There was no clear cut diagnosis of thyroid eye diease and an orbital biopsy was considered. An MRI was requested for preoperative planning which revealed the extraocular muscles to be of normal size. The biopsy was subsequently cancelled. The radiology team retrospectively noted that the patient had been in down-gaze during the CT, looking toward the radiographer’s control room, giving another false positive of extraocular muscle enlargement.
Several studies have shown that the ocular position influences the size of the extraocular muscles, specifically the thickness and volume of the muscles increases on contraction.2-4 We recommend that the interpretation of extraocular muscle size on radiological imaging should be accompanied by an assessment of the ocular position to minimise the risk of unnecessary orbital biopsy. Local discussion with radiology departments regarding the possibility of target fixation during scans may also be warranted.
1. Eade EL, Hardy TG, McKelvie PA, McNab AA. Review of extraocular muscle biopsies and utility of biopsy in extraocular muscle enlargement. Br J Ophthalmol. 2018 Jan 19. pii: bjophthalmol-2017-311147. doi: 10.1136/bjophthalmol-2017-311147.
2. Tian S, Nishida Y, Isberg B, Lennerstrand G. MRI measurements of normal extraocular muscles and other orbital structures. Graefes Arch Clin Exp Ophthalmol. 2000;238(5):393-404.
3. Clark, RA. Demer, JL. Changes in Extraocular Muscle Volume During Ocular Duction. Investigative Ophthalmology & Visual Science. 2016;57:1106-1111.
4. Loba P, Laudanska-Olszewska I, Majos A, Stefańczyk L, Broniarczyk-Loba A. Morphometric parameters of extraocular rectus muscles evaluated by dynamic-multipositional magnetic resonance. Eur J Ophthalmol 2015;25(5):373-378.
Dear Editor,
We have read with interest the paper by Klimova et al. Some statements in the paper are confusing and may even mislead the readers.
The authors claim in the survival section of the paper that: "Vitreoretinal lymphoma is a life-threatening disease, with a 5-year survival rate of 71% in our study". Vitreoretinal lymphoma (VRL) may affect vision, and in very advanced cases that we rarely see in recent years, may destroy the eye. However, VRL per se is not what that kills the patients, but the associated brain lymphoma or in some case the systemic lymphoma.
According to the results in this study (and the title of the paper), "Combined (local and systemic) treatment in patients with PVRL showed favorable results in comparison with local therapy alone (p=0.695). However, the statistical significance was not reached". It is no wonder that they claim that combined treatment is better than local treatment when they have 60% relapses. However, no other study of intra-vitreal (IVit) Methotrexate showed such a high relapse rate. In our experience, the relapse rate is extremely low with IVit methotrexate alone. Actually, in summarizing our ten years results we had no recurrence of the intraocular disease (2) and summarizing now our 20-year experience with 113 eyes, we had only two cases of recurrences (unpublished data). It is difficult to explain the poor results of the authors’ patients, using either intravitreal methotrexate al...
Dear Editor,
We have read with interest the paper by Klimova et al. Some statements in the paper are confusing and may even mislead the readers.
The authors claim in the survival section of the paper that: "Vitreoretinal lymphoma is a life-threatening disease, with a 5-year survival rate of 71% in our study". Vitreoretinal lymphoma (VRL) may affect vision, and in very advanced cases that we rarely see in recent years, may destroy the eye. However, VRL per se is not what that kills the patients, but the associated brain lymphoma or in some case the systemic lymphoma.
According to the results in this study (and the title of the paper), "Combined (local and systemic) treatment in patients with PVRL showed favorable results in comparison with local therapy alone (p=0.695). However, the statistical significance was not reached". It is no wonder that they claim that combined treatment is better than local treatment when they have 60% relapses. However, no other study of intra-vitreal (IVit) Methotrexate showed such a high relapse rate. In our experience, the relapse rate is extremely low with IVit methotrexate alone. Actually, in summarizing our ten years results we had no recurrence of the intraocular disease (2) and summarizing now our 20-year experience with 113 eyes, we had only two cases of recurrences (unpublished data). It is difficult to explain the poor results of the authors’ patients, using either intravitreal methotrexate alone or in combination with systemic high dose methotrexate.
In their discussion, the authors write that "Vitreoretinal lymphomas are considered to be systemic disease….". It should be emphasized that this disease is in most cases a unique type of lymphoma that affects immune-privileged organs: the brain, the eye, and the testis, and only in some cases (17% in our experience), the eye disease accompanies systemic lymphoma.
References
1) Klimova A, Heissigerova J, Rihova E, et al. Combined treatment of primary vitreoretinal lymphomas significantly prolongs the time to first relapse. Br J Ophthalmol 2018, doi: 10.1136/bjophthalmol-2017-311574
2) Frenkel S, Hendler K, Siegal T, et al. Intravitreal methotrexate for treating vitreoretinal lymphoma: 10 years of experience. Br J Ophthalmol 2008;92:383-8.
Sincerely Yours,
Jacob Pe'er, M.D.
Shahar Frenkel, M.D., Ph.D.
Ocular Oncology Service
Department of Ophthalmology
Hadassah – Hebrew University Medical center
Jerusalem, Israel
Dear Editor,
We thank Drs Sabherwal and Sood for their interest in our article.(1) We would like to respond to the interesting points they raise.
Table 3 presents our analyses of potential predictors of the correct diagnosis by rural doctors of diabetic retinopathy (DR) requiring treatment. Details on a number of the characteristics assessed in this table are presented in the first paragraph of the Results section, but not, as Drs Sabherwal and Sood point out, the proportion having received didactic training. Among the 28 rural doctors, 13 (46.4%) received such training and 15 (53.6%) did not.
In the Methods, we describe in detail the training received by ophthalmologists in the CREST (Comprehensive Rural Eye Service and Training) program. As described there, only two doctors per hospital (not all of whom examined patients in the current study) could attend the didactic phase of training at the Zhongshan Ophthalmic Center (ZOC). This is due to the limited number of ophthalmologists at a typical rural Chinese county hospital, and the heavy load of clinical duties. For more doctors to have left their facilities for the two-month didactic training would not have been practical. However, all ophthalmologists participating in the CREST network and in the current study received intensive hands-on training by medical retina experts from ZOC at their own facilities, which included the diagnosis and laser treatment of diabetic retinopathy (DR) as well as the u...
Show MoreDear Editor:
We read the article ‘Acute retinal toxicity associated with a mixture of perfluorooctane and perfluorohexyloctane: Failure of another indirect cytotoxicity analysis ’ by Coco et al. with great interest.[1] In this study, the authors reported on ocular toxicity due to perfluorooctane (PFO). They advised that the protocols used to determine the cytotoxicity of intraocular medical devices (which have been approved by the Organisation for the Standardisation of International Standards based on indirect methods) should be revised to ensure safety. We congratulate Coco et al.1 for their report because we believe that it has the potential to be a significant contribut or to the literature on this topic.
As is commonly known, PFO is saturated with PFO liquids, which have highly stable carbon-fluorine bonds that consequently make them inert. PFO has highly specific gravity, low viscosity, optical clarity immiscibility in water and interface tension towards water. It is regularly used in vitreoretinal surgery for complex retinal detachment repair because it displaces subretinal fluid and blood anteriorly, unfolds the retina in giant retinal tear cases and provides counter traction and retinal stabilisation during membrane peeling in eyes with proliferative vitreoretinopathy.[2,3] These properties make PFO useful for intraocular surgery. However, some limitations exist regarding PFO use as a long- term tamponade such as amaurosis, a lack of light perce...
Show MoreWe read with interest the masterly review of the neuro-ophthalmology of Behcet’s disease by Alghamdi et al (1). One small aspect we question. The authors state that in their patients with papilledema: “The diagnosis of CVT was documented in all patients by cerebral angiography and MRI showing partial or total lack of filling of at least one dural sinus and an elevated CSF opening pressure (>25 mm Hg) on lumbar puncture.” We have recently reported 8 BD patients with pseudotumor cerebri who did not have cerebral venous thrombosis (CVT) on MRI or MRV (2). Partial or total lack of filling of one venous sinus does not constitute the pathophysiological basis for intracranial hypertension; either the sagittal sinus must be occluded, or if only one transverse sinus is occluded then the other needs to be stenosed (3). It would be interesting to know what a review of their patient’s images by a neuro-radiologist would reveal.
1: Alghamdi A, Bodaghi B, Comarmond C, Desbois AC, Domont F, Wechsler B, Depaz R, Le Hoang P, Cacoub P, Touitou V, Saadoun D. Neuro-ophthalmological manifestations of Behçet's disease. Br J Ophthalmol. 2018 Apr 26. pii: bjophthalmol-2017-311334. doi: 10.1136/bjophthalmol-2017-311334.
Show More2: Akdal G, Yaman A, Men S, Çelebisoy N, Toydemir HE, Bajin MS, Akman-Demir G. Pseudotumor cerebri syndrome without cerebral venous sinus thrombosis in Behçet's disease. J Neurol Sci. 2017;383:99-100.
3: Halmagyi GM, Ahmed RM, Johnston IH. The Pseudo...
We have read with great interest the e-letter from Karakucuk et al. published in BJO responding to our paper titled ‘Acute retinal toxicity associated with a mixture of perfluorooctane and perfluorohexyloctane: Failure of another indirect cytotoxicity analysis ’ and we appreciate their positive appreciation of our research work.
Show MoreWe consider extraordinarily important that they have reported four more cases in their country, thus, supporting that acute toxicity cases were not a Spanish problem as has been stated by some retinologist at an European congress (Barcelona, September 2017).
We believe that this letter should encourage other colleagues from other countries from all over the world to report cases that certainly exist, according to non-official information from several companies.
We completely agree that the ISO (the International Organization for Standardization) guidelines to determine the in vitro cytotoxicity of intraocular medical devices should be immediately changed. These guidelines should adopt direct cytotoxicity methods to be performed with finished, sterilized, and ready for release products. The analytical method utilized should include cells or tissues close to those of the retina to guarantee specific sensitivity and should be scientifically validated.
We support the suggestion of increasing chemical research, because some companies are promoting chemical tests, as a “safety guarantee”, whose scientific validity and their direct...
Dear Editor,
It has come to our attention that three of the patients (# 2 and #3, half-brothers, and #10) from our paper in BJO (1) have been reported previously with video recordings but without eye movement recordings at age 0 to 3 years in symposium proceedings (1) prior to the eye movement recordings made at age 6-11 presented in this study.
Yours sincerely
Irene Gottlob
References
1) Pieh C, Simonsz-Toth B, Gottlob I. Nystagmus characteristics in congenital stationary night blindness (CSNB). Br J Ophthalmol 2008;92:236-240.
2) Simonsz HJ, Gottlob I, Kommerell G, Hergersberg M, Eriksson AW: Transient Infantile Upgaze Holding Insufficiency: Frühsymptom bei inkompl. cong. stat. Nachtblindheit und periventrikulärer Leukomalazie. Der Ophthalmologe 1998;95(suppl 1/1):178.
Dear Editor,
We read the article published by McKenna, et al (1) with great interest and laud them on the quality and design of their study. Screening for diabetic retinopathy in rural, low resource settings is the need of the hour, however models which are cost effective, yet provide intensive screening and continuum of care are limited. Keeping this in mind, we feel that there are a few points requiring further clarity in this article.
The odds-ratio calculated in table 3 displays the significant effect of didactic training on correct diagnosis by rural doctors. However, for the odds-ratio to be calculated, there would have been a comparison group of rural doctors who were not provided didactic training. The numbers of these doctors have not been mentioned, and no details have been provided as to whether they were given any basic level of training related to the program. In the results provided for comparison between rural doctors and the non-medical graders, it has not been made clear whether doctors who had not been provided didactic training were included. In that case, results presented in the study may have been biased towards the non-medical graders.
In the study, the arbitrator changed the grade for a high percentage of the cases, moreover, 33% of the images were not found to be of adequate quality. Hiring an arbitrator, re-checking the grading and assuring high quality images (2) through standard equipment and trained personnel would drive up...
Show MoreDear Editor
Show MoreWe read the above paper with much interest and welcome the review and analysis of trends in acanthamoeba keratitis – a very important complication from contact lens wear. The paper discusses the incidence of acanthamoeba keratitis at Moorfields Eye Hospital, a large tertiary referral centre.
We note an incidence of 18.5 cases per annum in 1997-1999, rising to a mean of 50.3 per annum in 2011-2016 and hence has been quite rightly quoted as almost a 3 fold increase in cases.
We would however suggest some caution when using those figures to state that there is an epidemic at present.
When one attempts to take into account the fluctuations in numbers of contact lens wearers with the United Kingdom per year and relate that to incidence of acanthamoeba keratitis one has a slightly modified view.1 There has been a steady increase in contact lens wear with figures from the ACLM estimating 4.2 million CL wearers in 2016. A figure has been created showing this relative incidence in a chart format.2
The figure represents the number of cases diagnosed at Moorfields divided by the number of contact lens users (rising from 1.6 million in 1992 to 4.2 million in 2016). Therefore the mean number of cases when adjusted for CL wearers is 8.5 per year with a standard deviation of 5.8, with 11.8 in 2015 and 14 in 2016.
Whilst there is still a significant rise in cases, compared to the mainly stable period of 1996-2010, the rates are still lower t...
I commend the authors on an excellent study looking into the stratification of impact of macular degeneration on vision-specific function in patients with early stage AMD vs. late stage AMD. I would like to report similar findings in a United States based population with data gathered from the National Health and and Nutrition Examination Survey 2007-2008 (NHANES) which is a population based cross-sectional survey that represents the non-institutionalized population of the United States.
As the author's of this study looked at the impact of early and late ARM on vision specific functioning, I assessed a similar question using the NHANES database, specifically looking at whether patients with early and late AMD reported insufficient correction with their currently prescribed glasses or contact lenses, another measure of vision-specific functioning. After survey weighting, the sample represented a US Population of 108,719,628 people with 3.2% of participants (N=3,992) self-reporting a diagnosis of age-related macular degeneration. This represented a weighted sample of 3,479, 028 people. Of these participants reporting a diagnosis of AMD, they had a higher odds of reporting trouble seeing even with correction with glasses or contacts (OR 2.98, Confidence Interval 1.87-4.6). This relationship was held valid when controlling for age, gender, diabetes, race, self reported glaucoma, self reported cataract surgery, retinal exam evidence of retinopathy, and smoking of...
Show MoreWe read the excellent paper ‘Review of extraocular muscle biopsies and utility of biopsy in extraocular muscle enlargement’ by Eade et al.1 with great interest. The authors reviewed the pathology in extraocular muscle biopsies performed over a 25-year period and reported the clinical and radiological features that might distinguish between benign and malignant diseases. As the authors note, it is imperative for the orbital surgeon to consider a muscle biopsy when the diagnosis is in doubt. With this in mind we would like to highlight two relevant cases of simulated extraocular muscle enlargement seen radiologically due to deviated ocular position rather than a pathological process related to the muscle itself. In both cases this confused the clinical picture and nearly resulted in needless surgery.
In case 1, a 42-year-old woman was referred to the oculoplastic clinic with diplopia, reduced vision in the right eye associated with retro-bulbar pain and facial paraesthesia. On examination, there was evidence of a right esotropia with a reduction of abduction (consistent with a 6th cranial nerve palsy) associated with reduced sensation involving the V1 and V2 distribution. Optic nerve function was normal. Investigations revealed an elevated serum IgG subclass 4 (1.18 g/L) and normal serum ACE. The MRI report confirmed increased girth of the right medial rectus muscle in conjunction with enlargement and pathological enhancement of right cavernous sinus extending into...
Show MoreDear Editor,
We have read with interest the paper by Klimova et al. Some statements in the paper are confusing and may even mislead the readers.
The authors claim in the survival section of the paper that: "Vitreoretinal lymphoma is a life-threatening disease, with a 5-year survival rate of 71% in our study". Vitreoretinal lymphoma (VRL) may affect vision, and in very advanced cases that we rarely see in recent years, may destroy the eye. However, VRL per se is not what that kills the patients, but the associated brain lymphoma or in some case the systemic lymphoma.
According to the results in this study (and the title of the paper), "Combined (local and systemic) treatment in patients with PVRL showed favorable results in comparison with local therapy alone (p=0.695). However, the statistical significance was not reached". It is no wonder that they claim that combined treatment is better than local treatment when they have 60% relapses. However, no other study of intra-vitreal (IVit) Methotrexate showed such a high relapse rate. In our experience, the relapse rate is extremely low with IVit methotrexate alone. Actually, in summarizing our ten years results we had no recurrence of the intraocular disease (2) and summarizing now our 20-year experience with 113 eyes, we had only two cases of recurrences (unpublished data). It is difficult to explain the poor results of the authors’ patients, using either intravitreal methotrexate al...
Show MorePages