Journal reading :

Outer Retinal Tubulation as a

Predictor of the Enlargement
Amount of Geographic Atrophy in
Age-Related Macular Degeneration
 Purpose

 To determine the prognostic value of outer retinal

tubulation (ORT) in the enlargement amount of
geographic atrophy (GA) in eyes with age-related
macular degeneration (AMD)
 Introduction

 2009  Zweifel,dkk pertama kali mengidentifikasi

outer retinal tubulation (ORT) pada penyakit yang
mengenai outer retinal dan RPE.
 Lesi ORT cabang stuktur tubuler pada outer
nuclear layer pada retina (OCT)daerah bulat/ovoid
hyporeflektif dgn batas hiperreflektif pada OCT B-
scan
 ORT  cedera sublethal pada fotoreseptor
hilangnya interdigitasi pada outer segment dg RPE
atau degenerasi pada RPE nya sendiri
 Introduction

 2011Wolff,dkk  ORT berhubungan dg giant cell

 Moussa,dkk GATE study  ORT sangat umum
dijumpai pada pasien dg GA, timbul 65% dari mata
pada atrophic region dan 26% pada mata di
junctional zone, yang tampaknya terkait dengan
pertumbuhan secara signifikan lebih cepat pada lesi
GA
 MAHALO study  mendaftarkan pasien dengan GA
sekunder pada AMD fase 1b / 2 uji coba secara acak
untuk mengevaluasi keamanan, kemampuan
toleransi dan efikasi pada lampalizumab
 Methods

 MAHALO study  143 subjek pada fase 1b/2

multicenter, randomized,single-masked, sham
injection controlled clinical trial of the
safety,tolerability,and evidence of activity of
lampalizumab in patients with GA associated with
AMD.
 Included evidence GA in both eyes resulting from
AMD only and without evidence of past or present
choroidal neovascularization
 Methods

 SD OCT multiple time points in both eyes 

Cirrus HD-OCT, 512 A-scan x 128 B-scan macular
cube protocol over 6x6-mm area centered on the
foveal center.
 Not included  GA extended outside the OCT scan
field at the baseline visit or if the signal strength was
poor (less than 6) at any point during study
 OCT Grading

 All OCT volume scans of the fellow (nonstudy) eye at

baseline and month 18 were reviewed by 2
independent, masked, certified OCT graders
 128 B-scans for each case level of the outer nuclear
layer reviewed carefullypresence of ORT
 Grader determine whether ORT was present,
severity or extent of ORT not quantified
 Result 2 graders were compare for dicrepant
casesmet in open adjudicationif not resolve 
final determination by the reading center director
(S.R.S)
 Grading of GA areas at the reading
centerperformed FDA-cleared advanced RPE
analysis tool, Cirrus HD-OCT based on sub-RPE
illumination
 Yehoshua dkkGA areas were analyzed after
applying a square root transformation (SQRT), the
enlargement amount did not show any dependence
on the baseline lesion size thus for all GA lesion,
SQRT was calculated and comparisons were made
based on this parameter also
 Statistical methods

 Compareenlargement GA vs enlargement SQRT of

GA a student t test
 Significance P<0.05 for the test
 Intraclass correlation coefficients, Bland-Altman
plots, and interrater agreement (κ value)assess
intergrader reproducibility
 Statistical analyses commercial software
(Statistical Package for Social Science version 19.0
SPSS,Inc,Armonk,NY: and Med-Calc version 12:
MedCalc sofware bvba; Mariakerke,Belgium)
 Results

 143 patients enrolled. 35 no month 18 visit  108

fellow eyes met the inclusion criteria and were
analyzed. In 61 of 108, GA lesion was multifocal
 Discussion

 ORTs were present in approximately 22% of eyes and

seemed to be associated with a slower growth of the
GA lesions.
 ORTs had a characteristic, generally radial pattern
and appeared to extend to the periphery of the
atropic lession as the lession enlarged.
 Important observation  presence of ORT seems to
be associated with slower growth of the GA lesions.
 areas of GA in eyes w/ORT generally were larger at
baseline compared with those w/out ORT
 SQRT applying this study the enlargement
amount of GA no longer was dependent on baseline
lesion size eyes w/ ORTs had lower enlargement
amount despite a larger initial lesion size.
 Moussa,dkk 43eyes presence ofORT associated
with larger GA lesions. In this study also (p=0,08).
Furthermore GA lesions with some evidence of
ORT (65% of their cases) may grow faster. Difference
in methods of ORT detection
 GAongoing processstarts loss of RPE cells and
choroid structures and eventually leads to
photoreceptor cell depletion
 Summary  eyes w/ORT, GA grows more slowly
than in eyes w/o ORT.
 ORT may have a protective effect on the growth of
these lesions and potentially are important
confounders that may need to be considered in
longitudinal studies of GA progression