Volume 10, Number 8
WELCOME to Review
of Ophthalmology's Retina
Online e-newsletter. Each month, Medical Editor Philip Rosenfeld,
MD, PhD, and our editors provide you with this timely and easily
accessible report to keep you up to date on important information
affecting the care of patients with vitreoretinal disease.
Initial Use of Aflibercept in Exudative AMD
Intravitreal aflibercept, a fusion protein with high affinity for vascular endothelial growth factor, offers an
alternative treatment for exudative age-related macular degeneration. Preclinical studies and early- and late-phase
clinical trials suggest that aflibercept's high-binding affinity may impart greater durability of activity and
increased efficacy compared to ranibizumab or bevacizumab.
The authors of the following retrospective review included 266 eyes of 249 patients with exudative AMD who
received aflibercept after treatment with bevacizumab and/or ranibizumab. They calculated mean central subfoveal thickness
on spectral-domain optical coherence tomography and mean logarithm of the minimal angle of resolution visual acuity at
one, three, six and 12 months after the first aflibercept injection. They also performed subgroup analyses in eyes
receiving at least five bevacizumab and/or ranibizumab injections in the six months prior to aflibercept and in
eyes receiving at least 10 injections in the 12 months prior to aflibercept.
Eyes received an average of 14.7 (range one to 43) ranibizumab and/or bevacizumab treatments prior to initiation
of aflibercept therapy, the authors reported. They also noted that mean central subfoveal thickness decreased from 300 to
275 µm at one month (p<0.001) and was maintained at six months. Mean logMAR visual acuity improved from
0.60 (Snellen equivalent 20/80) to 0.54 (20/70, p=0.01) at one month and was stable at 0.55 at six months
(Snellen equivalent 20/70, p=0.11, n=251). In 82 eyes receiving at least five injections in the six months prior
to aflibercept treatment (average of 18.1 injections total), the central subfoveal thickness improved from 296 to
279 µm at one month (p<0.0001) and was maintained at six months (p<0.0001). Visual acuity did
not change (0.48 [20/61] at one month compared to baseline, 0.49 [20/62], p=0.634, and at six months 0.51
[20/65], p=0.601). In 50 eyes receiving at least 10 injections in the 12 months prior to aflibercept
treatment (average of 21.8 injections total), the mean central subfoveal thickness decreased by 17 µm at one month
(p=0.0007) and was maintained at six months (p=0.013). Again, VA did not change (0.46 [20/56] at one
month; baseline 0.44 [20/56], p=0.547; and 0.50 [20/63] at six months, p=0.2445).
Aflibercept is a valuable treatment alternative in patients previously treated with bevacizumab and/or
ranibizumab injections. The authors of the study observed stability of VA and anatomic improvement on spectral-domain
optical coherence tomography after initiation of aflibercept treatment in those preciously treated with ranibizumab
and/or bevacizumab injections every four to six weeks.
Source: Cho H, Weber ML, Shah CP, Heier JS. Initial utilization of aflibercept in exudative age-related
macular degeneration. Eur J Ophthalmol. 2014;24(4):576–581.
Anti-VEGF Treatment's Affect on Choroidal
Thickness Over Time in Patients With Wet AMD
The study below evaluated change in subfoveal choroidal thickness as measured by spectral-domain optical
coherence tomography in patients with wet age-related macular degeneration undergoing anti-vascular endothelial
growth factor therapy.
Patients with a diagnosis of wet AMD were retrospectively reviewed to identify those who had at least 12 months of
follow-up. The subfoveal choroidal thickness was manually measured from Bruch's membrane to the choroid-sclera
junction at baseline and last follow-up. Only cases in which the choroid was fully visible were included in
quantitative analyses. The SCT measurements were correlated with other characteristics including number and duration of treatments.
A total of 60 eyes of 47 patients with a follow-up of 23.8 months (SD 7.3) met study inclusion criteria, and 49 eyes of
40 patients received anti-VEGF treatment. Mean age was 83.7 years, and 52% were female. Treated eyes received a mean
of 7.8 (SD 7.3) intravitreal anti-VEGF injections. The subfoveal choroidal thickness at baseline was 126.7 µm
(SD 50.6) for untreated and 136.2 µm (SD 57.6) for treated eyes. The SCT showed a decrease over time in both
groups, with a mean rate of reduction of 6.0 µm (p<0.0002) in treated eyes and 3.6 µm
(p=0.3741) in untreated eyes. However, the change in subfoveal choroidal thickness did not differ between the
groups (p=0.5113), and did not correlate with the number of re-treatments (p=0.552), visual acuity at
baseline (p=0.618), or change in visual acuity over time (p=0.429).
Although choroidal thickness decreased over time in eyes with wet AMD, anti-VEGF therapy did not appear to accelerate
or otherwise alter this decline.
Source: McDonnell EC, Heussen FM, Ruiz-Garcia H, et al. Effect of anti-VEGF treatment on choroidal
thickness over time in patients with neovascular age-related macular degeneration. Eur J Ophthalmol. 2014;
Jul 18. [Epub ahead of print]. DOI: 10.5301/ejo.5000509.
Short-Term IOP Trends Following Intravitreal
Ranibizumab Injections for Wet AMD
In this open-label, parallel, randomized, controlled trial (EudraCT Number: 2010-023037-35), researchers aimed
to determine the effect of oral acetazolamide on lowering the peak and duration of intraocular pressure rise
in glaucoma and glaucoma suspect patients, following intravitreal injection of ranibizumab for wet age-related macular degeneration.
Twenty-four glaucoma or glaucoma suspect patients received either 500 mg acetazolamide or no treatment 60 to
90 minutes before 0.5 mg ranibizumab. The primary outcome measure was the difference in IOP immediately after injection
(T0) and five, 10 and 30 min following injection. The researchers used analysis of covariance to compare groups,
adjusting for baseline IOP, and the study was powered to detect a 9-mmHg difference at T0.
According to the researchers, the IOP at T0 was 2.3 mmHg higher in the non-treated group (mean 44.5 mmHg, range [19 mmHg
to 86 mmHg]) compared with the treated group (mean 42.2 mmHg, range [25 mmHg to 58 mmHg]), but was not
statistically significant after adjusting for baseline IOP (p=0.440). They observed that at 30 minutes, IOP was
4.9 mmHg higher in the non-treated group (mean 20.6 mmHg, range [11 mmHg to 46 mmHg]) compared with the treated group
(mean 15.7 mmHg, range (8 mmHg to 21 mmHg]). This was statistically significant after adjusting for baseline IOP
Although the primary endpoints were not reached, the study researchers concluded that 500 mg oral acetazolamide, 60 to
90 minutes before intravitreal injection, results in a statistically significant reduction in IOP at 30 minutes
post injection. Prophylactic treatment may be considered as an option to minimize neuroretinal rim damage in
high-risk glaucoma patients who are most vulnerable to IOP spikes and undergoing repeated intravitreal injections
Source: Murray CD, Wood D, Allgar V, et al. Short-term intraocular pressure trends following
intravitreal ranibizumab injections for neovascular age-related macular degeneration—the role of
oral acetazolamide in protecting glaucoma patients. Eye. 2014;Aug 1. [Epub ahead of print].
Switching to Intravitreal Aflibercept Injection
for Treatment of PCV Refractory to Ranibizumab
To clarify the efficacy of switching to intravitreal aflibercept injection to treat polypoidal choroidal
vasculopathy refractory to ranibizumab, this retrospective study examined 43 eyes of 42 patients (mean age,
76.5 years) with PCV treated with aflibercept (2 mg/0.05 mL).
A treatment history of three consecutive monthly intravitreal injections of ranibizumab as an induction phase followed by
a pro re nata maintenance phase over 12 months was seen for all patients. All patients were refractory to
ranibizumab (defined as having persistent subretinal or intraretinal fluid by optical coherence tomography and unchanged
or decreased visual acuity compared with the time of the first ranibizumab injection, despite receiving the last
three consecutive monthly intravitreal ranibizumab injections after 12 months).
The mean logarithm of the minimum angle of resolution best-corrected visual acuity levels (Snellen equivalent)
improved significantly (p=0.0074) from 0.38 (20/48) at baseline to 0.34 (20/43) three months after switching
to aflibercept (Month Three) (mean BCVA improvement, 0.47 line). The central retinal thickness decreased significantly
(p<0.0001) from 245 µm at baseline to 131 µm at Month Three. Of 30 eyes with polypoidal lesions at
baseline, the polypoidal lesions regressed completely in 15 eyes (50%) at Month Three.
It was concluded that administering intravitreal aflibercept injection for patients with PCV refractory to
ranibizumab maintained or improved visual acuity and reduced or eliminated exudative lesions and occluding polypoidal
lesions without adverse events with short-term follow-up.
Source: Saito M, Kano M, Itagaki K, et al. Switching to intravitreal aflibercept injection for
polypoidal choroidal vasculopathy refractory to ranibizumab. Retina. 2014;Jul 30. [Epub ahead of print].
Low-Luminance Visual Acuity and Microperimetry in AMD
Investigators in Australia sought to compare the effectiveness of low-luminance visual acuity and microperimetry
as functional measures in early stages of age-related macular degeneration in this prospective, cross-sectional study.
Participants consisted of 179 subjects with a clinical spectrum of non-neovascular AMD and 26 control participants.
The investigators measured best-corrected visual acuity, LLVA and microperimetric retinal sensitivity on one eye of
all participants. They calculated low-luminance deficit as the difference between LLVA and BCVA. They also
compared functional parameters between six clinical severity groups (from controls to non-foveal geographic atrophy),
and determined and compared the relationships and magnitude of these parameters. Main outcome measures were visual
acuity parameters (BCVA, LLVA and LLD) and central retinal sensitivity.
Best-corrected visual acuity, LLVA and central retinal sensitivity were reduced significantly for all AMD clinical
severity groups when compared with control participants (p≤0.002), except for those with drusen between 63 and
125 µm (p≥0.107). However, LLD was not significantly different from control participants in all groups
(p≥0.073), except in the non-foveal GA group (p=0.008). According to the investigators, a
significant positive relationship between central retinal sensitivity and LLD (r=0.613; p<0.001), but
not BCVA, suggests that there is a trend for LLVA to detect a greater extent of functional deficit than BCVA in eyes
with increasingly poorer retinal sensitivity. However, the results of the linear regression models estimated central
retinal sensitivity to be 6.1, 3.7 and 5.1 standard deviations less than normal by the time BCVA, LLVA and LLD,
respectively, were two SDs less than normal.
To conclude, in early stages of AMD, LLVA did not detect a greater extent of functional deficit than BCVA when compared
with control participants. Although there was a trend for LLVA to be more effective at detecting foveal deficits than BCVA
in eyes with increasingly poorer retinal sensitivity, both visual acuity measures were much less sensitive compared with microperimetry.
Source: Wu Z, Ayton LN, Guymer RH, Luu CD. Low-luminance visual acuity and microperimetry in age-related
macular degeneration. Ophthalmology. 2014;121(8):612–1619.
Link Between Vasodilators, Blood Pressure-Lowering Medications and AMD
Scientists examined the association of vasodilator and anti-hypertensive medication use with the incidence
of age-related macular degeneration in this longitudinal population-based study that included persons aged 43 to
86 years living in Beaver Dam, Wisc., from 1988 through 1990.
They performed examinations every five years over a 20-year period. There were 9,676 total person-visits over the course
of the study. Status of AMD was determined from grading retinal photographs and the incidence of AMD was the main outcome measure.
The scientists reported that the five-year incidence of early AMD over the 20-year period was 8.4%; for late AMD,
it was 1.4%; for pure geographic atrophy, it was 0.6%; for exudative AMD, it was 0.9%; and for progression
of AMD, it was 24.9%. While adjusting for age, gender and other factors, using a vasodilator (hazard ratio [HR], 1.72;
95% confidence interval [CI], 1.25 to 2.38), particularly oral nitroglycerin (HR, 1.81; 95% CI, 1.14 to 2.90),
was associated with an increased risk of early AMD. Using an oral beta-blocker was associated with an increased hazard
of incident exudative AMD (HR, 1.71; 95% CI, 1.04 to 2.82), but not pure GA (HR, 0.51; 95% CI, 0.20 to 1.29)
or progression of AMD (HR, 0.92; 95% CI, 0.67 to 1.28) over the 20-year period.
To conclude, use of vasodilators is associated with a 72% increase in the hazard of incidence of early AMD, and use
of oral beta-blockers is associated with a 71% increase in the hazard of incident exudative AMD. If these findings
are replicated, it may have implications for care of older adults because vasodilators and oral beta-blockers are drugs
that are used commonly by older persons.
Source: Klein R, Myers CE, Klein BE. Vasodilators, blood pressure-lowering medications, and age-related
macular degeneration. Ophthalmology. 2014;121(8): 1604–1611.
Photoreceptor Layer Changes Overlying Drusen in
Eyes With AMD Associated With VMT
To investigate by spectral-domain optical coherence tomography changes of photoreceptor layers over drusen in cases
of dry age-related macular degeneration associated with vitreomacular traction, clinical examination,
fluorescein angiography, fundus photography and SD-OCT data were retrospectively studied for a consecutive series of
27 patients with drusen, pseudodrusen and VMT. Control groups of 32 patients with VMT without drusen and 34
patients with drusen and pseudodrusen without VMT were also studied.
The examination revealed disruption of the line corresponding to the inner segment ellipsoid (ISel), previously called
inner segment/outer segment junction, of photoreceptor layer, and development of cystoid edema in signiﬁcantly
higher incidence in VMT associated with drusen group. It was noted that 22 out of 32 eyes with VMT and drusen
(68.75%) had disrupted ISel, compared to eight out of 37 (21.6%) control eyes with drusen only and to 12 out of
37 (32.4%) control eyes with VMT only. Chi-square analysis showed significant association between drusen and
pseudodrusen on fovea, VMT and localization of ISel disruption. The changes of the ISel were mainly found in the area
that corresponded to VMT. The SD-OCT revealed drusen throughout the macula and discontinuation of ISel only in the fovea
in four of 32 (12.5%) eyes with VMT, whereas none of 37 control eyes with drusen only had similar appearance.
The drusen in association with the cystoid macular edema induced by vitreous traction contribute to the photoreceptor
layer defect overlying drusen in the fovea. In addition, the number of drusen and pseudodrusen was increased in the area
of the vitreous traction compared to the peripheral retina.
Source: Theodossiadis PG, Theodoropoulou S, Stamatiou P, et al. Photoreceptor layer changes overlying drusen
in eyes with age-related macular degeneration associated with vitreomacular traction. Eur J
Pseudodrusen and Choroidal Thickness
The authors of the study below sought to determine the relationship between pseudodrusen as evidenced by the presence
of subretinal drusenoid deposits and choroidal thickness using a multimodal imaging approach.
They analyzed two sets of data. The first set was composed of consecutive patients older than 60 years with either
high myopia or pseudodrusen. The authors calculated correlations between the subfoveal choroidal thickness and the
presence of pseudodrusen. They obtained the second set of data from previously published data examining 90 consecutive
eyes with dry age-related macular degeneration so they could analyze the relationship between pseudodrusen and
subfoveal choroidal thickness.
According to the study authors, there were 96 eyes of 53 patients in the first data set, 36 (67.9%) were female and
17 (32.1%) were male. There were 34 patients (61 eyes) in the high myopia group and 19 patients (35 eyes) in the
primary pseudodrusen group. The authors noted that the mean age of the primary pseudodrusen group was 83.7 years and that
of the high myopia group was 74.9 years—a difference that was significant (p<0.001). Of the 61 eyes in
the high myopia group, they determined that only three (4.9%) had pseudodrusen and zero had conventional drusen. In
the primary pseudodrusen group, all had pseudodrusen by definition, but 28 (80%) also had conventional drusen.
Moreover, the mean subfoveal choroidal thickness was 181.7 µm (median, 147; interquartile range, 65 µm to
225 µm) in the primary pseudodrusen group and 59 µm (median, 36; interquartile range, 21 µm to 90 µm)
in the myopic group. Generalized estimating equation analysis showed that eyes with pseudodrusen had thicker
subfoveal choroidal thickness than eyes without, a result driven by the high myopia group. In the second set of data,
while the absolute number of eyes with pseudodrusen had a choroidal thickness between 201 µm and 250 µm,
the proportion with pseudodrusen was higher in eyes with thinner choroids, with a broad peak between 50 µm and
The authors concluded that their results are not consistent with a simple cause or consequence relationship
between pseudodrusen and choroidal thinning, but rather with a third yet unknown factor impacting both the
pseudodrusen appearance and the choroidal thinning in susceptible populations. The reasons for the relative lack of
drusen and pseudodrusen formation in high myopes need to be ascertained.
Source: Mrejen S, Spaide RF. The relationship between pseudodrusen and choroidal thickness.
Change in Subfoveal Choroidal Thickness
Following Intravitreal Ranibizumb for Idiopathic CNV
Researchers investigated changes in subfoveal choroidal thickness after intravitreal injections of ranibizumab for
idiopathic subfoveal choroidal neovascularization in the following prospective, consecutive case series study.
They included 16 patients with unilateral idiopathic subfoveal CNV and treated all eyes with a single intravitreal
injection of 0.5 mg ranibizumab, followed by as-needed dosing. They also measured subfoveal choroidal thickness
using enhanced-depth imaging optical coherence tomography.
The mean total follow-up time was 4.9 ± 1.5 months, and the follow-up after the last intravitreal ranibizumab
injection was 4.4 ± 1.3 months, the researchers reported. In the treated eyes, they found that the subfoveal
choroidal thickness decreased significantly from 354 ± 84 µm at baseline to 328 ± 79 µm at one
month later (p<0.001) and reincreased (p=0.02) to 342 ± 75 µm at the final visit
(p=0.15 versus baseline value).
Change in subfoveal choroidal thickness was marginally (p=0.11) associated with the change in retinal
foveal thickness. In the contralateral unaffected eyes, the subfoveal choroidal thickness did not change significantly
during follow-up (p=0.76).
In patients with unilateral idiopathic subfoveal CNV, the study researchers found that intravitreal ranibizumab therapy
was associated with a thinning of an abnormally thick subfoveal choroid, marginally in association with a parallel
decrease in retinal foveal thickness. It remained elusive whether the choroidal thinning was due to a direct
pharmacological effect of ranibizumab or whether it was secondary due to the foveal retinal thinning. In view of
the significant differences in subfoveal choroidal thickness between affected eyes and unaffected contralateral eyes
at baseline and in view of the significant therapy-associated decrease in subfoveal choroidal thickness, the potential
role of subfoveal choroidal thickness as an additional marker for the diagnosis and follow-up of idiopathic subfoveal CNV
and other neovascular maculopathies may be examined in future studies.
Source: Cao XS, Peng XY, You QS, et al. Subfoveal choroidal thickness change after intravitreal ranibizumab
for idiopathic choroidal neovascularization. Retina. 2014;34(8):1554–1559.
Retinal Sensitivity Assessed by Microperimetry
and Corresponding Retinal Structure and Thickness in Resolved CSC
In Korea, investigators examined the relationship between retinal sensitivity assessed by microperimetry and
retinal structural changes in patients with resolved central serous chorioretinopathy. They found that retinal
sensitivity was dependent on the status of the ellipsoid portion of the inner segments (EPIS) in patients with resolved
CSC and determined that the correlation between mean retinal sensitivity and mean central retinal thickness
was compatible with the point-to-point correlation between retinal sensitivity and the corresponding retinal point
The investigators performed spectral domain optical coherence tomography examination and MP tests in patients with
resolved CSC. They also performed point-to-point correlation between retinal sensitivity and corresponding retinal
structural changes using Pearson's correlation analysis. In addition, in a 1-mm zone in the central fovea, a
correlation was calculated between the mean retinal sensitivity and the mean CRT.
A total of 84 eyes were analyzed, the investigators reported. They noted that the total number of microperimetry test
points was 1,092 (84 eyes x 13 points). The mean retinal sensitivity and RPT of all test points were 13.53 ± 3.84 dB
and 208.6 ± 48.0 µm, respectively. The investigators also found that the retinal sensitivity and RPT
were significantly decreased in the test points with loss of the EPIS (p<0.0001). Furthermore, within the
1-mm foveal center zone, they found a significant correlation between mean retinal sensitivity and mean CRT
(r=0.432, p<0.0001) and between retinal sensitivity and the corresponding RPT (r=0.339, p<0.0001).
Retinal sensitivity was dependent on the status of the EPIS in patients with resolved CSC, the investigators concluded.
The correlation between mean retinal sensitivity and mean CRT was compatible with the point-to-point correlation
between retinal sensitivity and the corresponding RPT.
Source: Chung HW, Yung CM, Kim JT, et al. Retinal sensitivity assessed by microperimetry and
corresponding retinal structure and thickness in resolved central serous chorioretinopathy. Eye. 2014;Aug 1.
[Epub ahead of print]. DOI: 10.1038/eye.2014.185.
Relationship Between Epiretinal Proliferation
and Lamellar Macular Holes
Researchers in this retrospective observational case review aimed to describe the prevalence and imaging characteristics of
a distinct entity of epiretinal proliferation seen predominantly in association with lamellar macular holes, termed
lamellar hole-associated epiretinal proliferation (LHEP).
They reviewed 2,030 eyes of 1,104 patients with diagnoses including lamellar macular holes, full-thickness macular hole
and epiretinal membrane imaged with spectral domain optical coherence tomography from 2008 to 2013. The
researchers identified LHEP, defined on SD-OCT imaging as an epiretinal material of homogenous medium reflectivity, and
they qualitatively compared its features against conventional ERM using the SD-OCT data.
They found LHEP in 68 of 2,030 eyes (3.3%), of which 88.2% had lamellar macular holes and 11.8%
had full-thickness macular hole. They found LHEP in 60 of 197 eyes (30.5%) with lamellar macular holes and eight of
99 eyes (8.0%) with full-thickness macular hole. They did not detect LHEP in 1,734 eyes with ERM, which had no
inner retinal defects detectable on SD-OCT; however, LHEP appeared as a substantial material of homogenous
medium reflectivity on the epiretinal surface that demonstrated contiguity with the middle retinal layers and conformed
to the adjacent retinal anatomy. Of the eyes with LHEP and lamellar macular holes, 98% had splitting of the retina in
the region of Henle's fiber layer in the area immediately around the partial thickness hole, whereas 88% had
visible connecting tissue from the base of the lamellar hole to the proliferating epiretinal tissue. In contrast to ERM,
LHEP did not induce tractional effects such as distortion or edema of the underlying normal retinal tissue.
Morphologic stability was demonstrated in 97% of eyes containing LHEP in serial eye-tracked SD-OCT images for up to
63 months of retrospective follow-up.
According to the study researchers, SD-OCT imaging showed that a subset of patients with lamellar macular holes had
an epiretinal proliferation with medium reflectivity and no evidence of contractile properties that was contiguous
with layers of the mid-retina. This phenotype differs from conventionally described ERMs in appearance and induced changes
of the underlying retina. Given these distinct anatomical relationships, the presence of LHEP could affect surgical outcomes.
Source: Pang CE, Spaide RF, Freund KB. Epiretinal proliferation seen in association with lamellar macular
holes: a distinct clinical entity. Retina. 2014;34(8):1513–1523.
Impact of Exome Sequencing on the Phenotypic
Spectrum for ABHD12 Mutations
The authors of this case series sought to identify the genetic causes underlying autosomal recessive
retinitis pigmentosa (arRP) and to describe the associated phenotype.
Participants consisted of 347 unrelated families affected by arRP and 33 unrelated families affected by retinitis
pigmentosa plus noncongenital and progressive hearing loss, ataxia or both, respectively.
The study authors performed a whole exome sequencing (WES) analysis in two families segregating arRP. A mutational
screening was performed in 378 additional unrelated families for the exon–intron boundaries of the ABHD12 gene.
To establish a genotype–phenotype correlation, individuals who were homozygous or compound heterozygotes of mutations
in ABHD12 underwent exhaustive clinical examinations by ophthalmologists, neurologists and otologists. DNA sequence
variants, best-corrected visual acuity, visual field assessments, electroretinogram responses, magnetic resonance imaging
and audiography were the main outcome measures.
After a WES analysis, the authors identified four new mutations: p.Arg107Glufs*8; p.Trp159*; p.Arg186Pro; and p.Thr202Ile
in ABHD12 in two families (RP-1292 and W08-1833) previously diagnosed with nonsyndromic arRP, which co-segregated with
the disease among the family members. They detected another homozygous mutation (p.His372Gln) in one affected
individual (RP-1487) from a cohort of 378 unrelated arRP and syndromic RP patients. After exhaustive clinical examinations
by neurologists and otologists, the four affected members of the RP-1292 had no polyneuropathy or ataxia, and
the sensorineural hearing loss and cataract were attributed to age or the normal course of the RP, whereas the
affected members of the families W08-1833 and RP-1487 showed clearly symptoms associated with polyneuropathy, hearing
loss, cerebellar ataxia, RP and early-onset cataract (PHARC) syndrome.
In conclusion, null mutations in the ABHD12 gene lead to PHARC syndrome, a neurodegenerative disease
including polyneuropathy, hearing loss, cerebellar ataxia, RP and early-onset cataract. This study allowed the authors
to report five new mutations in ABHD12. This is the first time missense mutations have been described for this
gene. Furthermore, these findings are expanding the spectrum of phenotypes associated with ABHD12 mutations ranging
from PHARC syndrome to a nonsyndromic form of retinal degeneration.
Source: Nishiguchi KM, Avila-Fernandez A, van Huet RA, et al. Exome sequencing extends the phenotypic
spectrum for ABHD12 mutations. Ophthalmology. 2014;121(8):1620–1627.
Retinal Blood Flow's Impact on OAG Patients
With and Without Diabetes
To evaluate the impact of retinal blood flow on optic nerve head morphology in patients with open-angle glaucoma with
and without diabetes mellitus, 66 patients with OAG (14 with DM, 52 without DM) were assessed at baseline and at
three-year follow-up for retinal capillary blood flow using confocal scanning laser Doppler and ocular structure
using Heidelberg retinal tomography and optical coherence tomography.
Change in retinal tissue with zero blood flow in the superior and inferior retina was found to have a strong correlation
with ONH changes in diabetic patients (r≥0.90, p≤0.03); however, no relation was found in the
nondiabetic cohort. There were also significant changes in inferior mean flow that strongly correlated with changes in
cup area (r=0.97, p=0.0029), cup/disc area ratio (r=0.96, p=0.0070), linear cup/disc ratio
(r=0.93, p=0.0172), rim area (r=−0.97, p=0.0036) and rim volume (r=–0.95, p=0.0084) in
diabetic patients only, while changes in the superior mean flow were only significantly associated with cup area
(r=–0.30, p=0.0498), cup volume (r=–0.36, p=0.0178) and rim volume (r=0.35, p=0.0193)
in nondiabetic patients.
In this cohort of patients with OAG, changes in retinal capillary blood flow correlated more strongly with changes in
ONH morphology in patients with DM than in those without DM. These data suggest that changes in retinal blood flow may
play a larger role in glaucomatous ONH progression in patients with OAG with DM.
Source: Lee E, Harris A, Siesky B, et al. The influence of retinal blood flow on open-angle glaucoma
patients with and without diabetes. Eur J Ophthalmol. 2014;24(4):542–549.