Displaying 1-10 letters out of 510 published
Real life visual improvements with anti vascular endothelial growth factor treatment for wet age-related macular degeneration - Absolute or relative?
We congratulate Holz et al.1 on their most important contribution to anti-vascular endothelial growth factor therapy in neovascular age-related macular degeneration (n-AMD). We think it is important to note that their main finding "visual acuity improved until about day 120; thereafter visual acuity changes were not maintained" does not contradict the findings of the MARINA2 [Ranibizumab Vs sham injection] clinical trial. We have previously re-evaluated3 the published results of the MARINA study to assess the absolute risk reduction (The absolute difference of outcome between experimental - i.e. ranibizumab treated - and control participants in the MARINA trial). This being the approach specified in The ABPI Code of Practice4 Clause 7; Information, Claims and Comparisons "Referring only to relative risk, especially with regard to risk reduction, can make a medicine appear more effective than it actually is. In order to assess the clinical impact of an outcome, the reader also needs to know the absolute risk involved. In that regard relative risk should never be referred to without also referring to the absolute risk. Absolute risk can be referred to in isolation." We set out in the graph below our evaluation of mean letter change from baseline (visual acuity change) derived from MARINA Figure 2 A results page 14262. The published change in letter score is at 3 month intervals rather than for each monthly injection as our efforts to acquire the raw data from the authors of the MARINA study2 have been unsuccessful. The best we can do is to show the letter change for the ranibizumab treated patients (we have confined our analysis to 0.5 mg group) letter score is in green, sham injection is in blue and the difference between the groups is in pink - this being the absolute risk reduction at every time we have data for. Our re-analysis seemingly confirms Holtz's findings1; ranibizumab is apparently most beneficial in the initial stages of treatment of n-AMD and visual gains cease between 3 - 6 months.
Figure 1 - Green line - Ranibizumab treated patients (0.5mg) - change in letters read since last injection. Blue line - Sham-injection treated patients - change in letters read since last injection. Pink line - Absolute risk reduction (The arithmetic difference between the Ranibizumab and sham groups for each 3-monthly time point.)
We note that Holtz and colleagues presented the mean change in visual acuity score after start of anti-VEGF as their primary endpoints. Our graph demonstrates the change in visual acuity score since previous visit and we note the striking resemblance in that both the analysis plots a very similar graph. While the patient demographics include the various subsets of n-AMD, we could not find any mention of visual acuity outcomes for these subset groups of patients. As MARINA showed visual benefits (stabilization or improvement of letters read) due to Ranibizumab treatment was achieved in only 27.6% of patients, we ask the authors if they are able to predict likely responders based on any base-line characteristics that would distinguish them from non-responders. Also would the authors be able to share if available their analysis of change in visual acuity from the previous visit. This could help in the early identification of those patients unlikely to benefit either prior to treatment or as the treatment progresses and avoid exposing patients unlikely to benefit to the risks of treatment.
1. Frank G Holz, Ramin Tadayoni, Stephen Beatty et al. Multi-country real-life experience of anti-vascular endothelial growth factor therapy for wet age-related macular degeneration.Br J Ophthalmol doi:10.1136/bjophthalmol-2014-305327
2. Philip J. Rosenfeld, M.D., Ph.D., David M. Brown, M.D., Jeffrey S. Heier, M.D. et al. for the MARINA Study Group. N Engl J Med 2006; 355:1419-1431.
3. B. Ramasamy, S Tiew, J Wason, L Clearkin . Absolute Risk Reduction and Natural Frequencies of Ranibizumab treatment in neovascular Age-Related Macular Degeneration (nvAMD). Poster and rapid fire presentation, Oxford Ophthalmological Congress ( 7/7/2015)
4. ABPI Code of Practice for The Pharmaceutical Industry https://www.bsped.org.uk/resources/docs/ABPIguidelines
Conflict of Interest:
Amniotic membrane graft to conjunctival flap in treatment of non-viral resistant infectious keratitis: a randomised clinical study
Dear Editor; We have read the article entitled "Amniotic membrane graft to conjunctival flap in treatment of non-viral resistant infectious keratitis: a randomised clinical study" by Abdulhalim et al. with interest.1 The authors compare the results of bipedicle conjunctival flap and cryopreserved amniotic membrane graft in the treatment of non-viral infectious keratitis resistant to medical treatment. We want to express our reservation about using amniotic membrane in the acute stage of fungal keratitis. The main immune mechanism against fungal keratitis depends on neutrophils.2 Karthikeyan et al. revealed that neutrophils constitute the vast majority (90%) of cellular infiltrates in fungus-infected human corneas.3 In the course of the anti-fungal immune activity reactive oxygen species secreted through the infected tissues play very critical roles. Furthermore, the balance between the host oxidant and the fungal anti- oxidant substances has been studied in order to decrease hyphal survival. Besides that; the balance between the host oxidant and the fungal anti- oxidant substances has lately been discussed to be targeted for diminishing hyphal survival.2 On the other hand, Lockington et al. recently reported that amniotic membrane can scavenge reactive oxygen species because of abundant hyaluronic acid.4 Besides, amniotic membrane may suppress immune defense by absorbing live inflammatory cells into its stroma and force them to apoptosis.5 Therefore, we suppose that antioxidant and anti-inflammatory properties of amniotic membrane could be objectionable during the acute phase of fungal keratitis in which fungicidal activity is essential. We propose that amniotic membrane transplantation should be delayed until the infection is limited to a certain location.
Conflict of Interest:
Response to " Recovery of photoreceptor inner and outer segment layer thickness after reattachment of rhegmatogenous retinal detachment"
We read with great interest the study" Recovery of photoreceptor inner and outer segment layer thickness after reattachment of rhegmatogenous retinal detachment" by Terauchi G, et al. Authors concluded that thickness of inner segment layer (20.4 +/- 5.0 microns) at one month after surgery was significantly less than fellow eye (28.9 =/- 2.9 microns). However, we know that the axial resolution of Spectral Domain(SD)-OCT is approximately 5 microns i.e. one pixel on the scan image would represent for 5 microns. This would lead to a difference between the outer segment measurements in operated eye and fellow eye in the range of 1-2 pixels, leaving very little room for error. Although, coefficient of repeatability for total macular thickness in Diabetic Macular Edema was found as high as 9 micron. The measurement error and coefficient of repeatability of outer segment and inner segment measurements using SD-OCT is still not known. Keeping this in account, would the results still remain statistically significant? Hence, if measurements were taken by Adaptive optics-OCT with axial resolution of 3micronthere would be greater reliability of measurements and results compared to SD-OCT especially considering smaller measurements like outer and inner segment layer thickness.
We keenly wait authors' reply.
1. Terauchi, G., et al., Recovery of photoreceptor inner and outer segment layer thickness after reattachment of rhegmatogenous retinal detachment. Br J Ophthalmol, 2015. 99(10): p. 1323-7. 2. Sohn, E.H., et al., Reproducibility of diabetic macular edema estimates from SD-OCT is affected by the choice of image analysis algorithm. Invest Ophthalmol Vis Sci, 2013. 54(6): p. 4184-8. 3. Miller, D.T., et al., Adaptive optics and the eye (super resolution OCT). Eye (Lond), 2011. 25(3): p. 321-30.
Conflict of Interest:
Genetic Testing for Chromosomal Aberration in Choroidal Melanoma
The authors have investigated the and compared the chromosome 3 aberrations of Choroidal melanoma (CM) as determined by multiplex ligation probe amplification (MLPA) or microsatellite analysis (MSA)in intra ocular tumor biopsies with those results obtained from subsequent endoresection/enucleation of the same Choroidal melanoma. However few points need clarification from the authors: 1. Since the investigators used few markers on chromosome 3, technically speaking the use of the word "Monosomy" is not appropriate to describe the generic findings. This is at best can be called "Partial monosomy" or even better, just describe the chromosome 3 locations of the deletions or chromosome 8 duplications. 2. There are better genetic techniques currently available to detect chromosomal deletions(s) and/or duplication(s) than multiplex ligation probe amplification (MLPA) or micro-satellite markers. For example, array comparative genomic hybridization (arrayCGH) high definition can be used to screen the full genomic for chromosomal abnormalities and even detect deletion(s) and/or duplication(s) as small as 10 Kb in size. The 100 ng of DNA which was used by the investigators for MLPA can be easily used for arrayCGH with small alterations to the protocol. This would make the results more comprehensive and may able to detect other alterations on other chromosomes. 3. The use of microsatellite markers to measure chromosomal abnormalities (duplication or deletion) is not appropriate. Microsatellite markers, if informative, can give you whether the tested individual is homozygous or heterozygous for a particular allele. They are not design to give you a quantitative answer and the peak height cannot be used for quantitative measure. 4. It will be great if the authors can elaborate on the genes encompassed in the deleted areas of chromosome-3 and how those genes may contribute to the development and/or metastatic effect on the melanoma. For example, are those genes involved in suppressing the tumor? or do they play some other role ? 5. In Table-2, the authors list 13 patients with Chr3 loss vs. 12 patients with no chr3 loss, can we actually use the deletion(s) on chr3 as a genetic marker for choroidal melanoma?
Conflict of Interest:
response to: 3D printed reproductions of orbital dissections: a novel mode of visualising anatomy for trainees in ophthalmology or optometry
We read the article '3D printed reproductions of orbital dissections: a novel mode of visualising anatomy for trainees in ophthalmology or optometry' by Adams JW. et al with great interest. The authors have successfully identified the need for experience handling and navigating through anatomical material to understand clinical ophthalmology. Furthermore, they have brilliantly created a means for this teaching to occur due to the difficulties obtaining cadaveric specimens, and the similar issues and expense of using plastinated models.
We were particularly interested in the preparation of the orbital dissections, and the choice of views to optimise the teaching value of the prosections. In the paper, it is stated quite rightly that 'it is essential to optimise the number of features displayed' (1). Given the authors' expertise in recreating the best from the cadaveric specimens to generate models, we would like the authors' opinion on how best to conduct an ophthalmic anatomy teaching session for students using approximately ten cadaveric heads which we will be running next year. What do the authors think would be the most important teaching aims, and how do the authors recommend specimens should be approached to maximise educational effectiveness? Furthermore, other than using techniques outlined in their paper to create the best views for models, are there any other ways in which we should take advantage of this privileged access to cadaveric tissue?
We would very much appreciate some advice and guidance with regards to this, and once again we commend the authors for this innovative method of teaching dissection.
References: 1. Adams JW, Paxton L, Dawes K, Burlak K, Quayle M, McMenamin PG, 3D printed reproductions of orbital dissections: a novel mode of visualising anatomy for trainees in ophthalmology or optometry, Br J Ophthalmol, 2015; 99(9): 1162-7
Conflict of Interest:
Re:Significance of hyper auto fluorescent (HAF) ring in choroidal neovascularization (CNV) in Age related Macular Degeneration (AMD)
Dr. Sagar and colleagues made reference to our paper "Significance of the Hyperautofluorescent Ring Associated with Choroidal Neovascularization in Eyes Undergoing Anti-VEGF therapy for Wet Age-Related Macular Degeneration", and pointed out the fact that they did not find a statistically significant difference in subretinal fluid (SRF) between eyes with and without a hyperautofluorescent ring (HAF) in their studied population.
We would first like to thank Dr Sagar et al. for their interest in our publication and in this newly reported autoflourescence phenomenon, which as was mentioned, is quite common among eyes diagnosed with neovascular AMD. Our rigorous data collection, measurements (including vertical and horizontal SRF extend, as well as SRF area) and analysis led to our results showing that the HAF ring had a positive correlation with baseline subretinal fluid and outer retinal disruption. Similar to their findings, our study did not show a statistically significant association with visual acuity.
Despite our thorough research on this topic, we agree that more work is indicated on this subject to fully understand the meaning and importance of the HAF ring.
William R. Freeman, MD Distinguished Professor and Director UCSD Jacobs Retina Center Vice Chairman Department of Ophthalmology, UCSD Shiley Eye Center 9415 Campus Point Drive La Jolla, CA 92093-0946
Tel: 858 534 3513 Fax: 858 534 7985
Conflict of Interest:
GRADES and DSA with respect to cancer risk following irradiation in childhood
We thank the authors for their prompt reply and do want to thank them for this wonderful paper which definitely serves as an excellent continuing professional development(CPD) module for us and will also be used by many CPD providers immediately after its publication
But another CPD module one engages in, is the GRADE system. And that has set me thinking trying to fill my learning gaps and the following is just my reflection in an attempt to improve my own understanding and I add that I realise that I could be completely wrong
The GRADE system can be used to grade the quality of evidence and strength of recommendations for diagnostic tests or strategies. (BMJ 2008;336:1106) which entails that "Inferring from data on accuracy that a diagnostic test or strategy improves patient-important outcomes will require the availability of effective treatment, reduction of test related adverse effects or anxiety, or improvement of patients' wellbeing from prognostic information"
Vascular malformations may be single vessel form ( arterial, capillary, lymphatic or veinous) or combined. Their flow characteristics may give a clue as to whether there is going to be an involution or not. The clinical characteristics are also important and Orbital LMs are reported to cause proptosis in 85%, ptosis in 73%, and restrictive eye movements in 46% of patients (Tunc M, Sadri E, Char DH. Orbital lymphangioma: an analysis of 26 patients. Br J Ophthalmol 1999; 83:76 - 80.). There is also a real risk of bleeding in such cases .Hence a diagnostic modality to be used may include one which gives maximum information in terms of whether vision can be potentially lost, extra ocular muscles are involved or not and if one needs to intervene surgically , then what are the planes involved; in addition to the fact whether bleeding is already present and in presence of bleeding an angiography hardly gives any information . One definitely doesn't want to make the patient spend money over multiple imaging modalities and would want the modality to be safe and repeatable and the repeat imaging comparable to look for changes in size ,homogeneity and other issues like evidence of inflammation, post procedure bleeding or infection and inflammation.So one tends to do an MRI in my opinion and I agree that it is open to interpretation since as an ophthalmologist I would love to look at extra ocular muscle involvement and possibility of amblyopia and would want to institute therapy based on prognosis which in turn is based on imaging.. A digital subtraction angiography thus becomes a secondary investigation which needs to be carefully selected keeping in mind risks both present and future besides economic considerations of a second test which is invasive and needs radiation which may potentially cause cancers
We do know that even after meticulous extensive surgical ligation of feeder , we do get recurrences and also have complications like perioperative haemorrhage(1) . Both these conditions do need follow up imaging at times . We have been following the reports of success with transarterial embolisation and do realise that some authors do a repeat digital subtraction angiography to check for resolution (2)
We realise that it may not be possible to scientifically conclude that a modality is a gold standard or the preferred treatment modality unless we evaluate the resolution of lesions by follow up imaging to prove that the same imaging shows complete resolution of malformation in the long term and that would be risky with a digital subtraction angiography since even the first imaging or treatment is associated with radiation risks which in itself is under investigation for leukaemia and head cancers which are projected even for CT scan in childhood
It has been suggested that " Use of CT scans in children to deliver cumulative doses of about 50 mGy might almost triple the risk of leukaemia and doses of about 60 mGy might triple the risk of brain cancer" and so ", radiation doses from CT scans ought to be kept as low as possible and alternative procedures, which do not involve ionising radiation, should be considered if appropriate." (3)
The risk of leukemia is reported highest from head scans for children younger than 5 years of age at a rate of 1.9 cases per 10,000 CT scans (4)
The dose for digital subtraction angiography can be high (5)
For the imaging of cerebral vessels, the effective dose according to some authors is calculated as 0.67 mSv for CTAngiography(CTA) and 2.71 mSv for Digital subtraction angiography(DSA) . For the imaging of cervicocerebral vessels, the effective dose is 4.85 mSv for CTA and 3.60 mSv for DSA. The maximum absorbed dose (milligray) for skin, brain, salivary glands, and eyes is 166.2, 73.5, 35.6, and 21.8 mGy for DSA and 19.0, 16.9, 20.4, and 14.8 mGy for CTA, respectively.
Various authors have studied risks and projected risks of head cancer and leukaemia with CT radiation (6) (7) (8)
As early as 2009 it has been estimated that 29000 cancers in future may be caused due to CT Scan with 4000 cancers due to head CT with this being more for radiation in children (9)
And so we wonder what would the strategy be, for reimaging , in case some of these kids do come back with recurrent swelling which may be inflammatory /infection /haemorrhage or simply recurrence because inflammation may stimulate lymphatic memory and regrowth (10)
Some authors have looked at the utility of 4 D imaging instead of repeat DSA even for small recurrences with small flow in brain AVMs (11) and found that the " diagnostic accuracy of 4D MRA for residual brain AVM compared with DSA, reached a sensitivity of 73.7%, specificity 100%, positive predictive value 100%, and negative predictive value 78.3%" (11) and so I wonder if this can be used to study the residual effects scientifically over a long term in case repeated imaging is necessary. I wonder if the GRADES approach is justified herein.
As far as the issue of anemia is concerned ,we know that inequalities exist in all human societies, even so-called "egalitarian" ones and I quote an American report that "An estimated 20 percent of American children will have anemia at some point in their childhood"(12) and another that states "Most children with mild anemia have no signs or symptoms" and even the BMJ best practices reports that "It is estimated that 3% of men and 8% of women in the UK have iron deficiency anaemia" and that Infants and adolescents have an increased risk as a result of high demand related to growth spurts besides the fact that " Microangiopathic hemolytic anemia (MAHA), has also been described with large capillary hemangiomas of the periocular region'wherein the erythrocytes are destroyed from coagulation, or are sheared or fragmented by high pressure forcing them through the abnormally small vessels of the hemangioma" (13) and unless an imaging is done one doesn't know whether the mass is a hemangioma or a lymphatic mass and some patients may benefit from ruling out an anemia at the outset without much damage done in the process
Besides it was long assumed anthropologically that iron deficiency anemia has marked effects on the flat bones of the cranium of infants and young children and that as the body attempts to compensate for low iron levels by increasing red blood cell production in the young, sieve-like lesions develop in the cranial vaults (termed porotic hyperostosis) and/or the orbits (termed cribia orbitalia)(14) and so if one does detect anemia there may be some reason though not strong enough to keep intracranial extensions in mind
I guess routine haemoglobin may fit into GRADES considering the low costs and relative safety in comparison to possible utility , but considering the issue of cancers with radiation in childhood routine digital subtraction angiography in every case may still need evaluation and we are still far away from a sweeping conclusion that sclerotherapy with digital subtraction angiography in all Paediatric cases should be the first line of treatment of orbital lymphatic malformations because we never do repeat angiography to prove resolution and neither are we sure whether the use of digital subtraction angiography is safe In terms of projected head and neck cancers and leukaemia which any radiation has the potential to cause in a child population ,where this condition is predominant
We agree to the wonderful results presented , but object to the conclusion of stating that sclerotherapy should be a first line of treatment of orbital malformations without long term efficacy scientifically proven by repeat imaging and long term risk of cancers with radiation associated with this being evaluated and discussed because sclerotherapy as is mutually agreed is dangerous without a digital subtraction angiography which being a radiation based modality carries with it the risks of cancers
References :- 1) Warrier S, Prabhakaran VC, Valenzuela A, Sullivan TJ, Davis G, Selva D.Orbital arteriovenous malformations. Arch Ophthalmol. 2008 Dec;126(12):1669-75.doi: 10.1001/archophthalmol.2008.501. 2) Sato K, Matsumoto Y, Kondo R, Tominaga T. Intraorbital arteriovenousmalformation treated by transarterial embolization: technical case report.Neurosurgery. 2011 Jun;68(2 Suppl Operative):383-7; discussion 387. doi:10.1227/NEU.0b013e31821522ec. 3) Radiation exposure from CT scans in childhood and subsequent risk of leukaemia and brain tumours: a retrospective cohort study.Pearce, Mark S et al.The Lancet , Volume 380 , Issue 9840 , 499 - 505) 4) Miglioretti DL, Johnson E, Williams A, Greenlee RT, Weinmann S, Solberg LI, Feigelson HS, Roblin D, Flynn MJ, Vanneman N, Smith-Bindman R. The use ofcomputed tomography in pediatrics and the associated radiation exposure andestimated cancer risk. JAMA Pediatr. 2013 Aug 1;167(8):700-7. doi:10.1001/jamapediatrics.2013.311. 5) Manninen AL, Isokangas JM, Karttunen A, Siniluoto T, Nieminen MT. A comparisonof radiation exposure between diagnostic CTA and DSA examinations of cerebral and cervicocerebral vessels. AJNR Am J Neuroradiol. 2012Dec;33(11):2038-42. doi:10.3174/ajnr.A3123. 6) Mathews John D, Forsythe Anna V, Brady Zoe, Butler Martin W, Goergen Stacy K, Byrnes Graham B et al. Cancer risk in 680?000 people exposed to computed tomography scans in childhood or adolescence: data linkage study of 11 million Australians 2013; 346 :f2360) 7) Huang WY, Muo CH, Lin CY, Jen YM, Yang MH, Lin JC, Sung FC, Kao CH (2014) Paediatric head CT scan and subsequent risk of malignancy and benign brain tumour: a nation-wide population-based cohort study. Br J Cancer 110(9): 2354-2360. 8) Meulepas JM, Ronckers CM, Smets AM, Nievelstein RA, Jahnen A, Lee C, Kieft M, Lameris JS, van Herk M, Greuter MJ, Jeukens CR, van Straten M, Visser O, van Leeuwen FE, Hauptmann M (2014) Leukemia and brain tumors among children after radiation exposure from CT scans: design and methodological opportunities of the Dutch Pediatric CT Study. Eur J Epidemiol 29(4): 293-301 9) Berrington de Gonz?lez A, Mahesh M, Kim KP, Bhargavan M, Lewis R, Mettler F, Land C. Projected cancer risks from computed tomographic scans performed in the United States in 2007. Arch Intern Med. 2009 Dec 14;169(22):2071-7. doi: 10.1001/archinternmed.2009.440. 10) Kelley PM, Connor AL, Tempero RM. Lymphatic vessel memory stimulated by recurrent inflammation. Am J Pathol. 2013 Jun;182(6):2418-28. doi: 10.1016/j.ajpath.2013.02.025. 11) Soize S, Bouquigny F, Kadziolka K, Portefaix C, Pierot L. Value of 4D MR angiography at 3T compared with DSA for the follow-up of treated brain arteriovenous malformation. AJNR Am J Neuroradiol. 2014 Oct;35(10):1903-9. doi: 10.3174/ajnr.A3982. 12) Irwin JJ, Kirchner JT. Anemia in children. Am Fam Physician. 2001;64(8):1379-1386. 13) Haik BG, Karcioglu ZA, Gordon RA, Pechous BP. Capillary hemangioma (infantile periocular hemangioma) Surv Ophthalmol. 1994;38(5):399-426. 14) Walker et al. 2009 "The Causes of Porotic Hyperostosis and Cribra Orbitalia: A Reappraisal of the Iron-Deficiency-Anemia Hypothesis" American Journal of Physical Anthropology.
Conflict of Interest:
Re:Orbital lymphatic malformation may shrink with treatment of anaemia
The authors thank Mr Moreker for his letter regarding our series. We agree that these are often complex cases and that each patient should be assessed holistically and discussed individually, ideally in a multidisciplinary setting. We do not check haemoglobin levels in all the patients referred to us, in part because severe anaemia in otherwise well children is rare in the UK population, but we agree that this should be done pre-operatively in children where anaemia is suspected. We acknowledge that a proportion of lymphatic malformations demonstrate a venous component and that it is vital to exclude any intracranial vascular connections before embarking on the injection of a sclerosing agent. In our series, contrast was injected into the malformation and digital subtraction imaging performed in every case prior to injection. Yours sincerely, Dr Alex M Barnacle BM MRCP FRCR Consultant Interventional Radiologist Great Ormond Street Hospital for Children London UK
Conflict of Interest:
Re:Re:Trephination size and success of big-bubble formation in deep anterior lamellar keratoplasty for keratoconus.
The response by Feizi et al is comprehensive and notable. But the condition could be simply explicated by a clear demonstration of actual data in a table representing DALK success-failure versus different trephination diameters. If the authors accept to publish these data, every reader would be able to deduce the practically applicable end result.
Conflict of Interest:
Outer retinal tubulation is a process of neurodegeneration
We read with interest the report by Espina et al(1) regarding changes occurring in outer retinal tubulation (ORT) during the course of intravitreal anti-VEGF treatment.(2) These authors retrospectively describe ORT changes observed during and after anti-VEGF treatment and correlated these changes to disease activity or presence of retinal fluid in 31 patients with neovascular age-related macular degeneration (AMD) with a median follow-up time of 11 months.(1) They noted ORT changes in 10 of 33 eyes with ORT detected at baseline and subsequent anti-VEGF treatment suggesting that some ORT contain vascular elements.(1) We address the latter issue here.
We recently showed (2, 3) histology and electron microscopy from 77 ORT cross-sections identified in 53 human donor eyes (40 exudative AMD and 13 geographic atrophy), and compared to spectral domain optical coherence tomography (SD-OCT) scans from 43 eyes with ORT from 34 patients. Additionally, we published a direct clinicopathologic correlation of ORT in one patient.(3) ORT is a gliotic formation of Muller cells and surviving photoreceptors, almost all cones, located in the outer nuclear layer.(2, 4) Cone photoreceptors degenerate by losing their outer segments, followed by inner segment retraction, with only the external limiting membrane formed by Muller cells left at the end-stage.(5) Thus, ORT undergo a natural evolution independent of anti-VEGF treatment, because our sample did not contain treated eyes, and we did not observe any vascular elements within these ORTs.
Others have reached similar conclusions about the ongoing degeneration of ORT as a natural progression of AMD, not secondary to anti -VEGF treatment,(6) and despite treatment with optimal visual outcomes, the prevalence of ORT has increased.(7)
To determine ORT dynamics longitudinally, a metric for measuring ORT changes, including size, shape, and eccentricity, in multiple closely spaced SD-OCT scans will be necessary. On the basis of extensive histology, ORT represents a distinctive process of neurodegeneration, observable in living patients, with a widely available imaging technology.
References 1. Espina M, et al. (2015) Outer retinal tubulations response to anti-VEGF treatment. The British journal of ophthalmology. 2. Schaal KB, et al. (2015) Outer retinal tubulation in advanced age- related macular degeneration: Optical coherence tomographic findings correspond to histology. Retina 35(7):1339-1350. 3. Litts KM, et al. (2015) Clinicopathological correlation of outer retinal tubulation in age-related macular degeneration. JAMA ophthalmology 133(5):609-612. 4. Curcio CA, Medeiros NE, & Millican CL (1996) Photoreceptor loss in age-related macular degeneration. Investigative ophthalmology & visual science 37(7):1236-1249. 5. Litts KM, Messinger JD, Freund KB, Zhang Y, & Curcio CA (2015) Inner segment remodeling and mitochondrial translocation in cone photoreceptors in age-related macular degeneration with outer retinal tubulation. Investigative ophthalmology & visual science 56(4):2243- 2253. 6. Gildener-Leapman JR, Srivistava S, Ehlers JP, & Kaiser PK (2015) Prevalence of outer retinal tubulation after anti-VEGF therapy for age- related macular degeneration. Ophthalmic surgery, lasers & imaging retina 46(3):345-348. 7. Dirani A, Gianniou C, Marchionno L, Decugis D, & Mantel I (2015) Incidence of outer retinal tubulation in ranibizumab-treated age-related macular degeneration. Retina 35(6):1166-1172.
Conflict of Interest:
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