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Recent eLetters

Displaying 1-10 letters out of 551 published

  1. Re: Response to AREDS supplements according to genetic factors: survival analysis approach using the eye as the unit of analysis

    We read with interest the article by Seddon, Silver, and Rosner [1], in which the authors studied progression from intermediate AMD to either geographic atrophy or choroidal neovascularization as a function of genetic risk and AREDS treatment assignment. This study of 4124 eyes by leaders in AMD genetic epidemiology is by far the largest series to analyze and validate a gene/treatment interaction. The authors show that CFH and ARMS2 interact statistically with AREDS treatment in opposing directions. The demonstrated allele dosage response to the AREDS formulation makes it logical that patients with the greatest CFH risk and the lowest ARMS2 risk would derive the least benefit from the AREDS formulation. Guided by these individual gene/treatment interactions, the authors investigated the interaction of composite genotype groups with the AREDS formulation. They defined "high" risk CFH as having 1 or 2 CFH risk alleles and "low" risk ARMS2 as having 0 ARMS2 risk alleles. Eyes of patients with 1 or 2 CFH risk alleles and with no ARMS2 risk alleles (33% of the study set) derive no benefit and had a trend toward increased CNV (HR 1.54) with a highly significant interaction coefficient (p=0.024). Knowing that one-third of individuals derive no benefit from the AREDS formulation is important. Millions of patients could avoid the cost and the occasional side effects associated with regular consumption of the AREDS formulation. The authors' decision to include patients with 1 CFH risk allele in the "high" CFH risk genotype group dilutes the impact of 2 CFH risk alleles. Given the identified dosage effect of CFH risk allele number, there is no scientific basis to fit the data to a Mendelian model of dominant genetics. Doing so potentially obscures the effects of the AREDS formulation in individuals at greatest risk of progression to CNV. We ask the authors to evaluate CNV risk in individuals with 2 CFH and 0 ARMS2 risk alleles treated with the AREDS formulation compared to placebo. This relatively straightforward analysis may reveal outcomes relevant for the optimal management of patients with AMD. Carl C. Awh, Brent Zanke 1. Seddon JM, Silver RE, Rosner B. Response to AREDS supplements according to genetic factors: survival analysis approach using the eye as the unit of analysis Br J Ophthalmol 2016;100:1731-1737 doi:10. 1136/bjophthalmol-2016-308624 Conflict of Interest Consultant, equity investor, ArcticDX (CCA) Employee, equity holder, Arctic DX (BW)

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  2. Re:Response to: Computer-aided design and three-dimensional printing in the manufacturing of an ocular prosthesis

    Response to e-letter to the editor

    We thank Dr. Mourits and co-workers for their interest and comments regarding our manuscript on impression-free three-dimensional (3D) printed anophthalmic socket, and appreciate their recognition of its value in the manufacturing of an ocular prosthesis.(1)

    Dr. Mourits and co-workers propose an alternative technique, impression mould through silicon injection in the anophthalmic socket, which is subsequently scanned with magnetic resonance imaging (MRI), and further 3D processed. This technique, however, renews the manual step of impression moulding, which reintroduces a non-digital procedure in the digital domain.

    We confirm the benefit of MRI over cone-beam computed tomography (CBCT) as radiation-free option.(2) However, we would like to highlight our concerns on the current use of MRI for the purpose of imaging the anophthalmic socket. First, spatial resolution of MRI is lower than CBCT, since MRI is characterized by geometric distortion produced by magnetic susceptibility, particularly at the air-tissue interface.(3,4) Second, longer acquisition times in MRI potentially result in more variable delineation.(5) Manual delineation in MRI, in contrast to computer- assisted delineation in CT, requires expertise and is time-consuming. Third, adequate MRI protocols and preferred coils for orbital scanning with high resolution and signal-to-noise ratio within reasonable measurement times are as yet not established.(6) By contrast, in CT, the process of delineation of soft tissue for calculation of orbital soft tissue volume is validated, reliable and accurate.(7) Finally, MRI in children requires general anaesthesia, which is associated with increased morbidity.(8)

    Continuous improvement in MRI imaging will help to further develop this innovative concept. We encourage Dr. Mourits et al to publish the data they shared on the use of a mould and special MRI orbital scanning.

    Bibliography

    1. Ruiters S, Sun Y, de Jong S, et al. Computer-aided design and three-dimensional printing in the manufacturing of an ocular prosthesis. Br J Ophthalmol 2016 ;100:879- 881.

    2. Brenner DJ, Hall EJ. Computed tomography--an increasing source of radiation exposure. N Engl J Med 2007;357(22):2277-84.

    3. Ludwig U, Eisenbeiss AK, Scheifele C, et al. Dental MRI using wireless intraoral coils. Sci Rep 2016;6:23301.

    4. Sumanaweera TS, Glover GH, Binford TO, et al. MR susceptibility misregistration correction. IEEE Trans Med Imaging 1993;12(2):251-9.

    5. Karlo C, Reiner CS, Stolzmann P, et al. CT- and MRI-based volumetry of resected liver specimen: comparison to intraoperative volume and weight measurements and calculation of conversion factors. Eur J Radiol 2010;75(1):e107-11.

    6. Georgouli T, James T, Tanner S, et al. High-resolution microscopy coil MR-Eye. Eye (Lond) 2008;22(8):994-6.

    7. Regensburg NI, Kok PH, Zonneveld FW, et al. A new and validated CT -based method for the calculation of orbital soft tissue volumes. Invest Ophthalmol Vis Sci 2008;49(5):1758-62.

    8. Cot? CJ, Wilson S. Guidelines for Monitoring and Management of Pediatric Patients Before, During, and After Sedation for Diagnostic and Therapeutic Procedures: Update 2016. Pediatr Dent 2016;38(4):13-39.

    Conflict of Interest:

    None declared

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  3. Intra ocular pressure control and fluctuation

    The effect of treatment with selective laser Trabeculoplasty

    Conflict of Interest:

    None declared

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  4. Impact of initial visual acuity on anti-VEGF treatment outcomes in patients with macular oedema secondary to retinal vein occlusions in routine clinical practice

    Impact of initial visual acuity on anti-VEGF treatment outcomes in patients with macular oedema secondary to retinal vein occlusions in routine clinical practice Dan Calugaru, Mihai Calugaru Department of Ophthalmology, Univ of Medicine Cluj-Napoca/Romania Re: Impact of initial visual acuity on anti-VEGF treatment outcomes in patients with macular oedema secondary to retinal vein occlusions in routine clinical practice. Wai et al. Br J Ophthalmol 2016;http:/dx.doi.org/10.1136/bjophthalmol-2016-308727.

    Dear Editor We would like to address several challenges arising from the study by Wai et al (1), which can be specifically summarized as follows:

    1. The study was retrospectively conducted with the existence of a selection bias because the choise of the specific anti-vascular endothelial growth factor (VEGF) agent was based on physician and patient preference. In addition, patients were retreated based on investigator determination of the presence of subretinal or intraretinal fluid as seen either by comprehensive ophthalmic examination and/or spectral-domain optical coherence tomography.

    2. The authors stated that there were relatively few numbers of ischaemic patients in their series although fluorescein angiography was performed in only 60.45% of the patients and no criteria used for the classification of patients as having ischaemic retinal vein occlusion (RVO) were indicated.

    3. The authors concluded that RVO patients with better initial visual acuities (VA) showed a nonsignificant change in VA and central subfield thickness (CST) over 12 months of treatment; conversely, patients with poor initial VAs showed dramatic improvements in Early Treatment Diabetic Retinopathy Study (ETDRS) letters and CST.

    4. In 2015, we documented for the first time (2), the impact of initial VA on bevacizumab (Avastin; Genentech, Inc., San Francisco, CA) treatment outcomes in patients with macular oedema secondary to acute central/hemicentral retinal vein occlusions. Although VA improvements at month 36 were significant in patients with both nonischaemic and ischaemic occlusions, the magnitudes of response to treatment were totally different, namely, an increase in VA of 17.5 letters (from 48.6 to 65.75 letters) in case of nonischaemic forms and of 26.81 letters (from 7.6 to 34.41 letters) in patients with ischaemic occlusions. The proportions of VA increases (from baseline values) were 36% in patients with better initial VA and 352.7% in patients having a poor initial VA, respectively. Such a comparison helped us to know that the intravitreal bevacizumab therapy was more effective in patients with ischaemic occlusions who required a significantly higher number of injections. In contrast with VA changes, the magnitudes of CST response to treatment were different, for example, a decrease of 300.49 microns in cases of nonischaemic and 351.33 microns in patients of ischaemic occlusions. However, the proportions of CST reductions (from baseline values) were similar in the nonischaemic and ischaemic groups (56.62% and 56.54%, respectively). So, the anatomic outcomes did not mirror the visual results mentioned above.

    Altogether, the assumption according to which patients with poor initial VA may benefit most from anti-VEGF suppression and vice versa, seems to be a somewhat paradoxical and counter-intuitive finding because patients with poor initial VA usually have advanced lesions which are difficult to be recovered. And yet, this assertion is logical since patients with low initial VA have a larger range of the interval in which VA can be improved in comparison with patients having a better initial VA with a more narrow interval and with small possibilities for improving. References 1. Wai KM, Khan M, Srivastava S, et al. Impact of initial visual acuity on anti-VEGF treatment outcomes in patients with macular oedema secondary to retinal vein occlusions in routine clinical practice. Br J Ophthalmol 2016; http:/dx.doi.org/10.1136/bjophthalmol-2016-308727. 2. Calugaru D, Calugaru M. Intravitreal bevacizumab in acute central/hemicentral retinalvein occlusions: three-year results of a prospective clinical study. J Ocul Pharmacol Ther 2015;31(2):78-86.

    Conflict of interest: None declared

    Conflict of Interest:

    None declared

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  5. Outcome of two-muscle surgery for large-angle intermittent exotropia in children - A comment

    We read the article titled "Outcome of two-muscle surgery for large- angle intermittent exotropia in children" by the authors Ki Won Jin and Dong Gyu Choi with great enthusiasm.1 The authors have compared the success of two muscle surgery for large angle (>=40 Prism Diopters (PD)) vs moderate-angle (>=20 and <30PD) intermittent exotropia. Neither of the two ranges described, include deviation between 30 to 39PD. Whether these deviations were excluded or this is a typographical error is subject to speculation. The range of exotropia in the large angle group was upto 70PD. Several prior studies have shown that success rates of two muscle surgery drop down significantly as the exotropia increases beyond 50PD2 and therefore three or four muscle surgery is recommended.3 Including such larger deviations skews the data and the chances of failure automatically increases in Group A of the study. We believe that a better comparison would have been between the moderate angle group and a second group of 35 - 50PD. None of the patients in the above study had symptomatic diplopia in lateral gaze or palpebral fissure changes at any postoperative visit in spite of performing large 9.5mm lateral rectus recession and 7mm medial rectus recession in at least some of the patients. This observation is unlike prior observations4 and our experience too with large recess-resect surgery. Lastly the authors have not compared the two groups in terms of refractive error which is an important factor leading to variations in preoperative measurement of deviation and the effect of surgery.5 Nonetheless we would like to congratulate the authors for conducting this important study that probably suggests that large angle intermittent exotropia warrants more than two horizontal rectus muscle surgery in order to achieve motor success in majority of patients.

    Conflict of Interest:

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  6. Response to: Computer-aided design and three-dimensional printing in the manufacturing of an ocular prosthesis

    With interest we have read the article of Ruiters et al.1 in which they present a 3 dimensional method for ocular prosthesis manufacturing. In our practice we also manufacture individual customized ocular prosthesis using 3D techniques. We confirm that this computer aided method improves prosthetic fitting and may aid the production process when translated into 3D prints. Our method does however differ on several points. First, in contrast to the authors, we make use of a mould, second we use MRI instead of cone beam CT. We agree with Ruiters et al.1 that the method of impression-moulding without other assistance frequently results in poor fitting prostheses. However, when assisted with 3D imaging a concise delineation of the socket can be made. The impression reflects the lines and curves of the posterior part of the socket in its most natural shape since it is introduced in a liquid state. The thickness of the mould depends on the amount of used silicone, hence it is not an adequate measure to use one-on-one for the thickness of the prosthesis. We believe this mistake is frequently made and may be the cause of bad fitting prostheses. We reject the argument of Ruiters et al.1 that introduction of moulding materials cause distortion of the socket, in fact we have experienced that a conformer, as used by the authors, does result in a distortion of the socket : when delineating the socket visualized on 3D images with a solid conformer in situ the delineation follows exactly the contours of the conformer. We use a special MRI program for orbital scanning taking only 5 - 6 minutes. In patients younger than 7 years scanning can be performed with general anesthesia, older patients can be instructed to lay still, head fixation eliminates motion artefacts as is also mentioned by Ruiters et al.1 MRI imaging avoids exposure to radiation, and MR- images will better depict the orbital soft tissues. In an upcoming paper we will expound our method.

    1. Computer-aided design and three-dimensional printing in the manufacturing of an ocular prosthesis. S?bastien Ruiters, Yi Sun, St?phan de Jong, Constantinus Politis, Ilse Mombaerts. Br J Ophthalmol 2016;100:7 879-881

    Conflict of Interest:

    None declared

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  7. Anatomical effects of dexamethasone intravitreal implant in diabetic macular oedema: a pooled analysis of 3-year phase lll trials

    Anatomical effects of dexamethasone intravitreal implant in diabetic macular oedema; a pooled analysis of 3-year phase lll trials Dan Calugaru, Mihai Calugaru Department of Ophthalmology, Univ of Medicine Cluj-Napoca/Romania Re: Anatomical effects of dexamethasone intravitreal implant in diabetic macular oedema: a pooled analysis of 3-year phase lll trials. Danis et al Br J Ophthalmol 2016;100:796-801.

    Dear Editor We would like to address several challenges arisen from the study by Danis et al (1) and which can be specifically summarized as follows:

    1. There was a selection bias owing to the inclusion in the study of both the treatment-na?ve patients and those with previous treatments (focal/grid laser, intravitreal steroid, and specific anti-vascular endothelial growth factor [VEGF] agents).

    2. Although the final central subfield retinal thickness (CSRT) values of the two dexamethasone implant (DEX implant; Ozurdex Allergan, Irvine, California, USA) groups (eg, 345.7 and 339 microns in the DEX implant 0.7 mg and DEX implant 0.35 mg groups, respectively) were significantly reduced in comparison with the sham group (398.8 microns) yet the structural outcomes of this study were poor. Of note, all these CSRT values are much more than the cutoff (252 microns) for the upper level of the normal CSRT (212 +/-20 microns) plus 2 standard deviations (2). The persistence of high values of the CSRT as well as the high proportions of study eyes with CSRT > 250 microns at the final visit (eg, 60.2 %, 58.7%, and 71.6% in the DEX implant 0.7 mg, DEX implant 0.35 mg, and sham groups, respectively) highlight unresolved macular edema due to insufficient macular deturgescence and indicate that the disease process is still active and progressive requiring further treatment with anti-angiogenic agents.

    3. The final unsatisfactory anatomic results of this study could be explained by the low frequency of injections (a median of four to five injections over a 3-year period) and the long-standing duration of diabetic macular oedema (DME) (between 23.6 and 25.9 months in the three groups of patients). These facts promoted the delayed occurrence of a permanent retinal capillaropathy owing to permanent breakdown of the inner and outer endothelial blood-retinal barriers. However, this condition is incurable due to the ischemic irreversible lesions to the macular retinal ganglion cell complex, close to the foveola, with macular oedema being a minor factor. The saw-tooth pattern of the profile of mean change in CSRT versus time highlights the fact that the authors have not taken into account the currently valid recommendations that the duration of ? 3-line improvement after DEX implant is typically 2-3 months (3), and that reinjections generally will be performed after 4-5 months (4). If these assertions had been considered, the design and outcomes of the present study would have been completely different.

    Altogether, regardless of the intravitreal pharmacotherapy chosen, namely, specific or nonspecific (DEX implant) anti-VEGF agents, the efficacy of treatment depends primarily on the promptness of the therapy after DME onset. Both groups of anti-VEGF substances provide similar rates of vision improvement but with superior anatomic outcomes and fewer injections in the DEX implant-treated eyes. However, more patients receiving the DEX implant lose vision mainly due to cataract.

    References 1. Danis RP, Sadda S, Li XY, et al. Anatomical effects of dexamethasone intravitreal implant in diabetic macular oedema: a pooled analysis of 3- year phase lll trials. Br J Ophthalmol 2016; 100:796-801. 2. Chan A, Duker JS, Ko TH, et al. Normal macular thickness measurements in healthy eyes using Stratus optical coherence tomography. Arch Ophthalmol 2006;124;193-198. 3. Kuppermann BD, Haller JA, Bandello F. Onset and duration of visual acuity improvement after dexamethasone intravitreal implant in eyes with macular edema due to retinal vein occlusion. Retina 2014;34:1743-1749. 4. Coscas G, Augustin A, Bandello F, et al. Retreatment with Ozurdex for macular edema secondary to retinal vein occlusion. Eur J Ophthalmol 2014;24:1-9.

    Conflict of interest: None declared

    Conflict of Interest:

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  8. Re:Comment on: Morphological features in anterior scleral inflammation using swept-source optical coherence tomography with multiple B-scan averaging

    Dear Editor:

    We thank Dr. Ebneter for his interest in our article.1 He pointed out that we included contralateral eyes of unilateral diseased eyes as control eyes and both eyes of bilateral affected eyes were included as diseased eyes. Accordingly, we performed additional analyses. We excluded contralateral eyes from control eyes and included only right eyes of bilateral affected eyes as diseased eyes. As a result, the average thicknesses of conjunctival epithelium, conjunctival stroma/episclera complex, and scleral stroma were 55.4?8.8, 288.0?44.4, and 434.2?60.1 ?m in the control group, 52.2?8.8, 320.7?48.6, and 455.8?43.4 ?m in diffuse episcleritis, 79.6?28.8, 450.7?138.3, and 469.5?41.7 ?m in diffuse scleritis, respectively. Significant differences could be found in conjunctival epithelium and conjunctival stroma/episclera complex among the three groups (p=0.002, 0.001, Kruskal-Wallis test), but not in scleral stroma (p=0.231). In diffuse scleritis, conjunctival epithelium and conjunctival stroma/episclera complex were significantly thicker than in controls (p=0.013 and 0.002). These results showed the same tendency as the original results.

    Second, Dr. Ebneter pointed out the weakness of the method, which is that the thickness is measured vertically but not perpendicularly to the ocular surface. We agree with him that this measurement method was crude and moderately inaccurate. Unfortunately, we could not measure the thickness in a direction perpendicular to conjunctival epithelium because SS-OCT was used for the posterior segment. Moreover, he indicated that the borders of the sclera in Figure 2B and 4B were vague. Indeed, it may not be easy to clearly distinguish scleral stroma and episclera. Severe thickening in the conjunctival stroma and episcleral layer may make the border indistinct. However, the point of this article, which is that thickening occurred mainly in the episclera rather than in the scleral stroma in diffuse scleritis, was meaningful, even if the measurements were crude.

    References

    1. Kuroda Y, Uji A, Morooka S, et al. Morphological features in anterior scleral inflammation using swept-source optical coherence tomography with multiple B-scan averaging. Br J Ophthalmol 2016. doi: 10.1136/bjophthalmol-2016-308561.

    Conflict of Interest:

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  9. Changing from pro re nata treatment regimen to a treat and extend regimen with ranibizumab in neovascular age-related macular degeneration

    Changing from pro re nata treatment regimen to a treat and extend regimen with ranibizumab in neovascular age-related macular degeneration Dan Calugaru, Mihai Calugaru Department of Ophthalmology, Univ of Medicine Cluj-Napoca/Romania

    Re: Changing from pro re nata treatment regimen to a treat and extend regimen with ranibizumab in neovascular age-related macular degeneration. Hatz and Prunte. Br J Ophthalmol 2016; http:/dx. doi.org/10.1136/bjophthalmol-2015-307299.

    Dear Editor We would like to address several limitations arisen from the interesting study by Hatz and Prunte (1) and which can be specifically summarized as follows:

    1. The article was retrospectively conducted with the existence of a selection bias due to the inclusion in the final analysis only those patients who completed treat and extend (TE) follow-up of 12 months. Of note, only patients with active disease during the last 3 months of the pro re nata (PRN) phase were transitioned to TE treatment.

    2. With the exception of data concerning the baseline choroidal neovascularization (CNV), there were no details on the anatomical types of neovascular maculopathy (CNV/serous and/or hemorrhagic detachment of the neurosensory retina or retinal pigment epithlium [RPE]/retinal hard exudates/subretinal and sub-RPE fibrovascular proliferation/disciform scar [subretinal fibrosis]), at baseline visit, as well as before and after switching from a PRN to a TE treatment regimen.

    3. There were no data referring to the proportion of eyes considered "dry" on optical coherence tomography as per criterion of central retinal thickness (CRT) < 320 microns (2), before and after switching to a TE algorithm.

    4. The comparative analysis of the visual and morphologic outcomes of the two treatment regimens was fairly inconclusive. Thus, there was a mean visual acuity (VA) gain of approximately 5 Early Treatment Diabetic Retinopathy Study (ETDRS) letters in comparison with the baseline VA at the end of the PRN phase; this value increased subsequently by an average of approximately 5 letters until the month 12 of the TE phase. The CRT decreased by a mean of 86 microns in relation to the baseline value, up to the end of the PRN phase; this CRT reduction increased thereafter by a mean of 35 microns until the month 12 of the TE phase. Importantly, during the TE period of this study, patients received approximately two more injections over a 12-month period than during 12 months of PRN treatment.

    5. Implementation of the 2-sequence, 2-period, 2-treatment algorithm design in which each patient was assigned to a sequence of treatment, did not provide the answer to the question which of the 2 treatment approaches was more efficiently. On the contrary, the disadvantages of such a study could not be avoided. Thus, the washout period, which is essential between periods of such a study in terms of aliased effects, was not precisely delimited and the impact of the significant carryover effects may be confounded with direct treatment effects, in the sense that these effects could not be estimated separately being able to bias the interpretation of data analysis.

    Altogether, regardless of the treatment approaches chosen (TE/PRN algorithm), the efficacy of therapy depends primarily on the promptness of the therapy after neovascular age-related degeneration diagnosis (3,4).

    References 1. Hatz K, Prunte C. Changing from pro re nata treatment regimen to a treat and extend regimen with ranibizumab in neovascular age-related degeneration. Br J Ophthalmol 2016; http:/dx. doi.org/10.1136/bjophthalmol -2015-307299. 2. Grover S, Murthy RK, Brar VS, and Chalam KV. Normative data for macular thickness by high-definition spectral-domain optical coherence tomography (spectralis). Arch Ophthalmol 2009;148-271. 3. Calugaru D, Calugaru M. Treat-and-extend intravitreal bevacizumab for branch retinal vein occlusion. Ophthalmic Surg Lasers Imaging Retina 2015;46:994. 4. Calugaru D, Calugaru M. Comment on:"Central retinal vein occlusion:modyfing current treatment protocols." Eye 2016; http:/dx.doi.org/10.1038/eye.2016.83.

    Conflict of interest: None declared

    Conflict of Interest:

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  10. Re:Outcomes of intravitreal anti-VEGF therapy in eyes with both neovascular age-related macular degeneration and diabetic retinopathy

    We thank Drs Calugaru M. and Calugaru D. for their interest in our article,1 and we welcome this opportunity to address their concerns. The purpose of our study was to investigate the outcomes of intravitreal antivascular endothelial growth factor (VEGF) therapy in eyes with both neovascular age-related macular degeneration (AMD) and diabetic retinopathy (DR) as higher levels of VEGF due to concomitant DR in eyes with active neovascular AMD may lead to a higher consumption of anti-VEGF molecules, thus impairing the efficacy of treatment.1 As pointed out, in our series we included patients that had undergone other treatments for DR, either before or during administration of anti- VEGF drugs for neovascular AMD. This is an obvious limitation of our retrospective study, even though all the patients included were treatment na?ve for anti-VEGF agents. We recorded that best corrected visual acuity, after a significant improvement at 1 year, returned to baseline values at the last follow-up visit, while mean central macular thickness (CMT) significantly decreased from 408 ?m to 335 ?m. As pointed out, these results may suggest that disease process could be still active and progressive requiring further treatment. 2 In fact, at the end of follow up, CNV was still active in 39% eyes, while 61% eyes developed an atrophic/fibrotic scar with no signs of activities. On the other hand, CMT could have been influenced by the two concomitant diseases, the diabetic retinopathy and the choroidal neovascularization. In particular, we cannot exclude that some patients underwent anti-VEGF treatment, DR-related macular edema. We agree that, a lot of cytokines, chemokines, and growth factors may be associated with DR pathophysiology.3,4 Further prospective studies should consider the effects of these molecules and the use of non-specific anti- VEGF substances which inhibits the up-regulation of the VEGF and suppresses the expression of the whole panoply of the proinflammatory and proangiogenic factors.

    References 1. Bandello F, Corvi F, La Spina C, et al. Outcomes of intravitreal anti- VEGF therapy in eyes with both neovascular age-related macular degeneration and diabetic retinopathy. Br J Ophthalmol 2016; http:/dx.doi.org/10.1136/bjophthalmol-2016- 308400. 2. Gover S, Murthy RK, Brar VS, et al. Normative data for macular thickness by high-definition spectral-domain optical coherence tomography (spectralis). Am J Ophthalmol 2009;148:266-271. 3. Sohn HJ, Han DH, Kim IT, et al. Changes in aqueous concentrations of various cytokines after intravitreal triamcinolone versus bevacizumab for diabetic macular edema. Am J Ophthalmol 2011;152:686-694. 4. Shah SU, Harless A, Bleau L, et al. Prospective randomized subject- masked study of intravitreal bevacizumab monotherapy versus dexamethasone implant monotherapy in the treatment of persistent diabetic macular edema. Retina. 2016 Apr 27. [Epub ahead of print]

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