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We read with interest the article by Seddon, Silver, and Rosner1, 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 an...
We read with interest the article by Seddon, Silver, and Rosner1, 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
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 a...
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.
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...
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.
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....
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.
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....
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
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.
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.
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 resul...
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.
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...
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.
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 a...
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]
We read with interest the article by Seddon, Silver, and Rosner1, 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 an...
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 a...
The effect of treatment with selective laser Trabeculoplasty
Conflict of Interest:
None declared
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...
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....
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....
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.
De...
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 resul...
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...
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 a...
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