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Retinal Degeneration Causes Diagnosis and Treatment
1st Edition Robert B. Catlin Digital Instant Download
Author(s): Robert B. Catlin
ISBN(s): 9781608764426, 1608764427
Edition: 1
File Details: PDF, 11.44 MB
Year: 2009
Language: english
Copyright © 2009. Nova Science Publishers, Incorporated. All rights reserved.
Copyright © 2009. Nova Science Publishers, Incorporated. All rights reserved.
 Eye and Vision Research Developments Series

RETINAL DEGENERATION: CAUSES,

DIAGNOSIS AND TREATMENT

No part of this digital document may be reproduced, stored in a retrieval system or transmitted in any form or
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 Eye and Vision Research Developments Series

Eye Cancer Research Progress

Edwin B. Bospene (Editor)
2008. ISBN: 978-1-60456-045-9

Non-Age Related Macular Degeneration

Enzo B. Mercier
2008. ISBN: 978-1-60456-305-4

Optic Nerve Disease Research Perspectives

Benjamin D. Lewis and Charlie James Davies (Editors)
2008. ISBN: 978-1-60456-490-7

New Topics in Eye Research

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2009. ISBN: 978-1-60456-510-2

Eye Infections, Blindness and Myopia

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2009. ISBN: 978-1-60692-630-7

Retinal Degeneration: Causes, Diagnosis and Treatment

Robert B. Catlin (Editor)
2009. 978-1-60741-007-2
Copyright © 2009. Nova Science Publishers, Incorporated. All rights reserved.
 Eye and Vision Research Developments Series

RETINAL DEGENERATION: CAUSES,

DIAGNOSIS AND TREATMENT

ROBERT B. CATLIN
EDITOR
Copyright © 2009. Nova Science Publishers, Incorporated. All rights reserved.

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New York
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Retinal degeneration : causes, diagnosis, and treatment / editor, Robert B. Catlin.

p. ; cm.
Copyright © 2009. Nova Science Publishers, Incorporated. All rights reserved.

Includes bibliographical references and index.

ISBN 978-1-60876-442-6 (E-Book)
1. Retinal degeneration. I. Catlin, Robert B.
[DNLM: 1. Retinal Degeneration. WW 270 R43805 2009]
RE661.D3R475 2009
617.7'35--dc22
2009001303

Published by Nova Science Publishers, Inc. 

  New York
 Contents

Preface vii
Chapter 1 Physiopathology of Retinal Degeneration in Rd1 Mouse Model
of Retinitis Pigmentosa: TGF-Β1, Proteinases
and Oxidative Stress Mechanisms 1
Satpal Ahuja, Poonam Ahuja-Jensen, A. Romeo Caffe,
Magnus Abrahamson, Per Ekstroma and Theo van Veen
Chapter 2 Progressive Retinal Dystrophies 43
Ilene Tsui, J. Mie Kasanuki and Stephen H. Tsang
Chapter 3 Usher Syndrome 61
Carmen Nájera, Elena Aller, Teresa Jaijo and José M. Millán
Chapter 4 Molecular Genetics of Norrie Disease, Familial Exudative
Vitreoretinopathy and Retinopathy of Prematurity 89
Barkur S. Shastry
Chapter 5 Genetic Risk Factors in Age-Related Macular Degeneration 107
Barkur S. Shastry
Chapter 6 Genetic Variations of ARMS2/HTRA1 Locus in 10q26.13
and Age-Related Macular Degeneration 119
Dequan Chen
Copyright © 2009. Nova Science Publishers, Incorporated. All rights reserved.

Chapter 7 Pharmacological Monotherapy for Neovascular Age-related

Macular Degeneration 131
Bradley T. Smith, Daniel P. Joseph and M. Gilbert Grand
Chapter 8 The Benefits and Risks of Cataract Surgery in Patients
with Age-Related Macular Degeneration 141
Dalia Zaliuniene and Vytautas Jasinskas
 vi Contents

Chapter 9 Early Detection and Diagnosis of Age-Related Macular

Degeneration: From Slit Lamp Examination to Advanced Imaging
Techniques and Psychophysical Tests 155
Michael Waisbourd, Yair Manor, and Anat Loewenstein
Chapter 10 Retinal Degenerations Associated with Systemic Drug Toxicity 191
Pedro Romero-Aroca, Baget-Bernaldiz and Alicia Traveset-Maeso
Chapter 11 Non-Rod Non-Cone Photoreception in Humans: Roles in Vision
and Disease 213
Farhan Husain Zaidi
Chapter 12 In Vivo Visualization of Photoreceptor Layer and Lipofuscin
Accumulation in Stargardt’s Disease / Fundus Flavimaculatus
by Optical Coherence Tomography 237
Giuseppe Querques, Domenico Martinelli, Lea Querques,
Gisèle Soubrane and Eric H Souied
Chapter 13 Visual Training in Retinitis Pigmentosa Patients: Neural Plasticity
and Function Recovery 249
Enzo M. Vingolo, Serena Salvatore, Pier Luigi Greng
and Paolo Limoli
Chapter 14 Serum-Free Retinal Explant Culture System and Comparative
Rescue Effects of LEDGF, GST, CNTF, BDNF, NGF, Bfgf
and Antioxidants in the Rd1 Mouse Model of Retinitis Pigmentosa 263
Satpal Ahuja, MVSc, Poonam Ahuja-Jensen, A. Romeo Caffé,
Maria Thereza Perez, Per Ekström and Theo van Veen
Chapter 15 Future Outlook in the Treatment of Age-Related
Macular Degeneration 301
Olli Arjamaa
Short Communications 311
Posterior Capsular Opacification in Retinitis Pigmentosa Patients 313
Enzo Maria Vingolo, Serena Salvatore, Sonia Cavarretta,
PierLuigi Grenga and Roberto Grenga
Copyright © 2009. Nova Science Publishers, Incorporated. All rights reserved.

Pedical Omental Transplant 323

V.K. Agarwal and P.S. Hardia
Antioxidants in Age Related Macular Degeneration 335
Pedro Durães Serracarbassa
Index 341
 Preface

Retinal tissue may degenerate for a number of reasons. Among them are: artery or vein
occlusion, diabetic retinopathy, R.L.F./R.O.P. or disease (usually hereditary). Retinitis
pigmentosa, retinoschisis, lattic degeneration, and macular degeneration are characterized by
progressive types of retinal degeneration. This new book presents the latest research in the
field.
Chapter 1 - The rd1 (retinal degeneration) mouse retina shows degeneration homologous
to a form of retinitis pigmentosa with a rapid loss of rod photoreceptors and deficiency of
retinal blood vessels. Due to Pde6brd1 gene mutation, β subunit of phosphodiesterase (PDE)
of rd1 retina has an inactive PDE which elevates cGMP and Ca2+ ions level. In vitro retinal
explants provide a system close to the in vivo situation, so both approaches were used to
compare the status of oxidative stress, transforming growth factor-β1
(TGF-β1), sialylation, galactosylation of proteoglycans, and different proteinases-
endogenous inhibitors systems participating in extracellular matrix (ECM)
remodeling/degeneration and programmed cell death (PCD)/apoptosis in wt and rd1 mouse
retinas.
Proteins and desialylated sulfated glucosaminoglycan parts of proteoglycans in ECM of
rd1 retina were, respectively, decreased and increased due to enhanced activities of
proteinases. Desialylation increases the susceptibility of cells to phoagocytosis/apoptosis,
decreased neurogenesis and faulty guidance cues for synaptogenesis. In vivo activities of
total proteinases, matrix metalloproteinase-9 (MMP-9) and cathepsin B were increased in rd1
retina on postnatal day 14 (PN14), -21 and -28, due to relatively lower levels of tissue
Copyright © 2009. Nova Science Publishers, Incorporated. All rights reserved.

inhibitor of MMPs (TIMP-1) and cystatin C, respectively. This corresponded with increased
in vitro secretion of these proteinases by rd1 retina. Cells including end-feet of Mueller cells
in degenerating rd1 retina showed intense immunolabeling for MMP-9, MMP-2/TIMP-1,
TIMP-2 and cathepsin B/cystatin C, and proteinases pool was increased by Mueller cells.
Intense immunolabeling of ganglion cell (RGC) layer for cathepsin B and of inner-plexiform
layer of both PN2/PN7 rd1 and wt retinas indicated importance of cathepsin B in
synaptogenesis and PCD of RGC.
Increased levels of TGF-β1 in vitro transiently increased the secretion of MMPs and
cathepsins activities by wt explants which activate TGF-β1 and remodel the ECM for
angiogenesis and ontogenetic PCD. Whereas, lower level of TGF-β1 and persistently higher
 viii Robert B. Catlin

activities of MMPs and cathepsins in rd1 retinas and conditioned medium, suggested that
proteinases degraded TGF-β1 and ECM and caused retinal degeneration.
Lower activities of glutathione-S-transferase and glutathione-peroxidase in rd1 retina
contribute to oxidative stress which damages membranes and increased the expression,
release/secretion of proteinases relative to their endogenous inhibitors. Participation of
oxidative stress in rd1 retinal degeneration was further confirmed from the partial protection
of rd1 photoreceptors by in vitro and/or in vivo supplementation with glutathione-S-
transferase or a combination of antioxidants namely lutein, zeaxanthin, α-lipoic acid and
reduced-L-glutathione. Treatment with combination(s) of broad spectrum proteinase
inhibitor(s) and antioxidants needs investigation.
Chapter 2 - Retinal degenerative diseases are the leading cause of irreversible blindness
in western countries today. Our knowledge of the underlying pathophysiology and hence,
targets for therapeutic intervention, are evolving, but still limited. While many retinal
degenerations are believed to have a multifactorial etiology, we now know that there is a
genetic component that is at least partially responsible for the clinical manifestations seen in
many of these diseases, such as retinitis pigmentosa and age-related macular degeneration
(AMD).
Chapter 3 - Usher syndrome (USH) is an autosomal recessive disease characterized by
hearing loss and retinitis pigmentosa (RP). It is both clinically and genetically heterogeneous
and its prevalence makes it the most common association of deafness and blindness of
genetic origin. From a clinical point of view, USH is categorized into three types. Usher type
I (USH1) is the most severe form and is characterized by severe to profound congenital
deafness, vestibular areflexia, and prepuberal onset of progressive RP leading to blindness.
Type II (USH2) displays moderate to severe hearing loss, absence of vestibular dysfunction,
and later onset of retinal degeneration. The less frequent type III (USH3) shows progressive
post-lingual hearing loss, variable onset of RP, and variable vestibular response. To date, five
USH1 genes have been identified. In the majority of populations the most commonly mutated
gene is MYO7A (USH1B), which represent 50–60% of the total USH1 patients, followed by
CDH23 (USH1D), PCDH15 (USH1F), USH1C, and USH1G. Defects in MYO7A also cause
autosomal dominant non-syndromic sensorineural deafness (DFNA11), autosomal recessive
deafness (DFNB2), as well as atypical forms of Usher syndrome, which are clinically similar
to Usher syndrome type III. Among the three genes implicated in USH2, mutations in the
USH2A gene account for 70–80% of the USH2 cases, and this gene is also implicated in
isolated RP without associated deafness. The other two implicated genes are VLGR1
Copyright © 2009. Nova Science Publishers, Incorporated. All rights reserved.

(USH2C) and WHRN (DFNB31). USH3 is rare except in some founder populations, USH3A
being the gene responsible for this type.
Our group has been working in the clinics, on the epidemiology and genetics of this
syndrome, carrying out the complete clinical study of each patient and the search for
mutations in the different implicated genes, to identify a genotype-phenotype correlation, and
to contribute to the understanding of the genetic basis of the disease, in order to establish a
rational therapy in a next future.
Chapter 4 - Blindness or visual impairment is a devastating health problem and has
always been a major public health concern. Many ocular disorders involve neovascularization
of the retina and it is the most common cause of blindness. Disorders such as familial
 Preface ix

exudative vitreoretinopathy (FEVR), Norrie disease (NDP), retinopathy of prematurity

(ROP), persistent fetal vasculature syndrome (PFVS) and Coats’ disease can cause blindness
in early childhood and all of them involve abnormal vascularization of the peripheral retina
and retinal detachment. Although the exact reason for the abnormal vascularization of the
peripheral retina is not completely understood, during the last decade rapid progress has been
made in identifying the genes and their variants responsible for these ocular disorders. As a
result, interestingly all of the above disorders are found to be associated with mutations in a
group of genes responsible for the highly regulated Wnt signaling pathway. This pathway is
well known in making decisive role in embryonic patterning, cell fate determination and
regulating ocular growth and development by activating the transcription of specific target
genes. However, the relationship between phenotype and genotype in hereditary retinal
diseases is still a mystery. It is not clear why certain genetic defects cause a more severe
clinical symptom in some patients while in others the same genetic alteration causes a less
severe phenotype. Although gene replacement therapy, prenatal diagnosis and carrier
detection have not been tried extensively for ocular disorders such attempts are now feasible
for many inherited eye disorders because of the availability of animal models. Additionally,
further investigations on the basic Wnt signaling mechanism may lead to a better
understanding of the retinal degeneration and novel therapeutic approach to prevent or treat
these debilitating blinding diseases. Thus, for patients and clinicians the future holds more
optimism than ever before.
Chapter 5 - Age-related macular degeneration (AMD) is a disorder of the retina, retinal
pigment epithelium (RPE) and choriocapillaris. It is a heterogeneous group of genetically
complex progressive degenerative disorder and causes changes in the macular region, that is
responsible for seeing fine details clearly. The condition is painless and is the leading cause
of irreversible blindness in the elderly population. The most common characteristics of AMD
are the development of drusen and atrophy of RPE (patchy loss of RPE). Heritability of AMD
ranges from 46-71% and it has a penetrance of 0.05% before the age of 50 years and 11.8%
after 80 years of age. The pathogenesis of the disorder and the biochemical pathways
involved are not understood. Epidemiological, familial aggregation and twin studies suggest
that genetic and environmental factors play an important role in determining the onset of
disease. Among environmental factors, smoking and age have been consistently found to be
associated with AMD. Over the past several years, linkage and association studies have
identified several chromosomal regions that are likely to predispose individuals to AMD.
Among these, the most consistently identified genetic loci lie on chromosomes 1q31 and
Copyright © 2009. Nova Science Publishers, Incorporated. All rights reserved.

10q26 regions. Molecular genetic analyses of chromosome 1q31 region have identified a
common variant (Y402H) in the complement factor H (CFH) gene as a major genetic risk
factor for AMD in Caucasian population. Subsequent association studies on chromosome
10q26 region have also revealed a common polymorphism (A69S) in the coding region of the
LOC387715 gene and a promoter polymorphism (-512 bp) in the adjacent (about 7 kb
downstream of LOC387715 gene) HTRA1 gene. The LOC387715/HTRA1 polymorphisms
are considered as second major risk factors contributing to AMD pathogenesis. These results
have been replicated by several independent studies in different populations. Additionally,
various forms of AMD are found to be associated with variations in factor B (BF) and
complement component 2 (C2) that are located on chromosome 6p. A comprehensive study
 x Robert B. Catlin

of variants at 3 loci suggests an independent contribution of three loci to disease risk and no
evidence of epistasis between CFH and LOC387715 genes has been reported. For other
candidate genes, variations did not account for a significant fraction of patients. Although
these studies have not provided any benefit for the treatment of the disorder, further research
on additional genetic and environmental factors may contribute to the better understanding of
the onset and progression of AMD. This may eventually result in better treatment and
diagnosis.
Chapter 6 - Age-related macular degeneration (AMD), a central retinal complex trait
disease, is involved with genetic and environmental risk factors. Chromosomal 10q26.13
region was linked to the risk of AMD by early family-based genome-wide scan studies, and
the AMD risk signal was first associated with three genes in the region, including PLEKHA1,
ARMS2 (hypothetical) and HTRA1. Later SNP association studies have locked the most
significant AMD-susceptibility signal in this region onto the locus of ARMS2 and HTRA1,
and two single nucleotide polymorphisms (SNP) in this ARMS2/HTRA1 locus – rs10490924
in the hypothetical ARMS2 exon 1 and rs11200638 in the downstream HTRA1 promoter
region have been consistently associated with AMD in different study cohorts across the
world, including Caucasian, Chinese, Indian and Japanese populations. This suggests that
either ARMS2 or HTRA1 or both play a critical role in AMD development. However, genetics
has not been successful in differentiating the roles of the two genes in AMD susceptibility
due to high or almost 100% linkage disequilibrium (LD) in this ~ 7 kb region. The
controversy over whether either one or both genes are a must in AMD development remains
un-resolved so far. To fully determine the roles of the two genes in AMD risk, we believe
that the following two lines of questions must be answered: (1) Is ARMS2 existent as a real
gene in nature? ESTs in the GenBank+EMBL+DDBJ database, 2 NIH-MGC clones and RT-
PCR amplified cDNA bands suggest that it can transcribe into an mRNA(s). Then what’s the
mRNA sequence(s)? Is it exactly like what NCBI database predicted? Is it encoding a native
protein(s)? Is the native protein exactly like what the database predicted? If yes, what’s the
normal function of the native protein? How genetic variations in ARMS2/HTRA1 locus affect
its function during AMD development? (2) Whether and how HTRA1 is involved in AMD
risk? No nonsynonymous coding SNPs but promoter region SNPs and other types of SNPs of
HTRA1 have been found to be associated with AMD, suggesting that HTRA1 expression
level change may be a mechanism for the involvement of HTRA1 in AMD risk if it has a role
in nature. It remains controversial as to whether the HTRA-rs11200638 risk allele A increases
HTRA1 expression due to the presence of reports with supporting and denying data.
Copyright © 2009. Nova Science Publishers, Incorporated. All rights reserved.

Nevertheless, how do all the genetic variations in ARMS2/HTRA1 locus possibly affect
HTRA1 expression level (increase, decrease or no effect)?
AMD is a central retinal disease that mainly causes the irreversible central vision
blindness in older individuals (more than 55 years old)[1;2]. In the United States, AMD leads
to significant visual impairment for approximately 7.5 million elderly Americans[3;4]. AMD
is known to be a complex trait involved with genetic and environmental risk factors. These
include: (a) three chromosomal loci – CFH in 1q32[5-24], ARMS2/HTRA1 in 10q26.13
[8;18;25-49] and C2/BF in 6p21.3 [3;50]; (b) biomarkers of systemic inflammation such as
C-reactive protein [51-56]; and (c) smoking [31;57-64]. Over half of the risk for AMD
appears to be explained by genetic factors with environmental and lifestyle exposures.
 Preface xi

Chapter 7 - A shift has occurred in the treatment options of choroidal neovascularization

(CNV) due to age-related macular degeneration (AMD). Prior to ocular photodynamic
therapy (PDT) the only available treatment was laser photocoagulation. The advantages of
PDT were limited to slowing the rate of visual acuity loss. However, compared with laser
photocoagulation this was accomplished with less collateral damage to the overlying retina.
Pegatanib sodium (Macugen), the first purely pharmacological treatment of AMD showed
similar efficacy to PDT and ushered in a new method of treatment for CNV. Pharmacologic
therapies directed at vascular endothelial growth factors (VEGF), the major stimulus for CNV
growth, have now become the standard of care. Ranibizumab (Lucentis) is a recently FDA-
approved monoclonal antibody to VEGF that can stabilize and even improve visual acuity in
a significant number of patients. Favorable results have also been reported for a related
monoclonal VEGF antibody, bevacizumab (Avastin). The following provides an overview of
current therapies used to treat CNV due to AMD.
Chapter 8 - Both cataract and age-related macular degeneration (ARMD) are not unusual
findings in the aging eye. They are two the most common causes of irreversible visual loss in
developed world. The number of cataract surgeries is steadily increasing in most of these
countries. However, the benefits (and risks) of cataract surgery in patients with ARMD are
uncertain. Some investigators found that cataract surgery benefits patients with ARMD,
ensuing in improved visual function and quality of life in most patients , whereas others
reported that in patients with ARMD, improvement in visual outcome after cataract surgery
can be limited. Furthermore, recent studies found even progression from early to late stages
of ARMD in eyes after cataract surgery.
There are several possible reasons that might explain, either individually or in concert,
the association between cataract surgery and late ARMD: 1) cataract and ARMD simply
share one or more common risk factors, including age, diet, light exposure, inflammation,
and/or genetic factors, 2) cataract surgery can increase photo-oxidative damage to the retina,
3) the surgery may also increase intraocular inflammation, 4) hypodiagnosis of ARMD in
persons with lens opacity.
However, it is not possible to draw an extensive conclusion concerning the effect of a
cataract surgery on the development of early ARMD or on the progression of pre-existing
ARMD, because in most of the previous studies, different study designs, classifications of
ARMD, and the length of follow-ups were used.
Currently, there is no conclusive evidence to support a relation between progression of
ARMD and cataract surgery. However, some investigators have concluded that there is
Copyright © 2009. Nova Science Publishers, Incorporated. All rights reserved.

certain evidence from observational studies to support an association between cataract

surgery and subsequent onset of late ARMD, respectively progression of early to late ARMD
Additional clinical trials with sufficient statistical power, a well-defined length of the
study period, an adequate control variables, such as age and severity of cataract or ARMD to
prove or disprove the reasons of possible influencing factors, such as types of lens,
intraocular inflammation, and genetic factors are needed to be assessed. A differential risk of
ARMD and differential response to cataract surgery due to genetic diversity of the patient
populations are still not reported.
 xii Robert B. Catlin

Conclusion. We must be selective and treat only the patients who are to get most benefit
from cataract surgery or who may have the lowest risk level for late ARMD. The
development of guidelines for the surgical management of this group of patients is needed.
Chapter 9 - Early detection of age-related macular degeneration (AMD), the leading
cause of blindness and visual impairment in the developed world, is now of utmost
importance in the era of preventive micronutrients and anti angiogenetic treatment strategies.
According to epidemiological studies, about 30% of adults above age 75 show signs of AMD
(Klein et al., 1992). Moreover, prevalence is expected to double in the coming decades,
coincident with the increase in the elderly population (Friedman et al., 2004).
Chapter 10 - Introduction. A variety of systemic drugs causes retinal toxicity, the visual
function effect in the major cases is minimal or reversible, nevertheless, permanent or
progressive visual loss may occur. In the present study we revised the literature of the
systemic toxicity drugs, and rapport the results of our experience as Retina and Oncologic
reference Center. Focusing special attention to the chloroquine, tamoxifen, and
aminoglycosids.
Methods. A search of the bibliographic databases (MEDLINE) was conducted; selected
relevant studies were scrutinized and included in the review. We revised also the patients
submitted to chloroquine , hydroxychloroquine, tamoxifen and other oncologic agents in our
Hospital and also revised all toxic retinal degenerations of several drugs in the last 20 years.
Results. We observed six different forms of retinal drug toxicity: disruption of the retina
and retinal pigment epithelium associated to chloroquine derivatives and oncologic drugs;
crystalline retinopathy associated most frequently to tamoxifen use; cystoid macular edema
with the use of nicotine acid, prostaglandin topical drugs and aminoglycosids; vascular
damage associated to cisplatinum , talc and oral contraceptives; retinal folds with use of
antibiotics , hydrocholothiazide and metronidazole; finally we may appoint two drugs that
causes visual disturbances produced by a probably retinal toxicity but without characteristic
fundus abnormalities as the digoxin and the methanol.
Conclusions. Although there are thousands of systemic medications, only a small number
produce retinal changes, but the extensively use of some agents as derivative chloroquine and
oncology agents, and the increasing use of intravitreal injections, the patients with retinal
toxicity degenerations may increase in the next future. Furthermore the mechanism by which
toxicity develops is not always understood, because retinal toxicity may occur when the agent
is used at therapeutic levels. In conclusion Ophthalmologists’ need to maintain a high
attention to the deleterious changes observed in a patients in treatment with systemic drug
Copyright © 2009. Nova Science Publishers, Incorporated. All rights reserved.

use.
Chapter 11 - The fascinating discovery of a new fundamental class of photoreceptor,
which is neither rod nor cone, in the inner retina of some mammals has recently been
complemented by parallel discoveries in humans. Studies using human subjects with rod and
cone dystrophies have unveiled the existence of a similar system of inner retinal
photoreception in rodless coneless humans to that in some mammals [Zaidi FH et al. Short-
wavelength light sensitivity of circadian, pupillary, and visual awareness in humans lacking
an outer retina. Current Biology 2007 December 18; 17(24): 2122-8]. These and related
studies and their significance are described in the first part of this chapter. The roles the
 Preface xiii

receptor is likely to have in retinal degenerations and functionally related conditions are
discussed in the second part of the chapter.
The novel receptor is a subgroup of retinal ganglion cells called photoreceptive retinal
ganglion cells (pRGC) or giant gangion cells, which reside in the inner retina and which in
distinction to classic (rod and cone) outer photoreceptors use melanopsin as its photopigment.
The pRGC receptor is the driver of the body’s neuro-endocrine circadian rhythms via
secretion of pineal melatonin which it directly regulates, it makes a substantial component to
pupillary reactions especially in humans, and it also contributes to behavioural alertness.
Of cardinal importance is that recently the pRGC has been shown in humans to mediate
conscious sight, a role for it that had not been described in animals. The response it elicits
can be markedly different to that found in blindsight.
Studies with rodless coneless humans, in whom vision is still found due to the
persistence of the pRGC response, create a major revision to existing models for
understanding visual perception. This is into a classic pathway which is found in the outer
retina and originates in rods and cones, and an alternate pathway arising from the inner retina
and which is driven by pRGCs. The latter can even function in the absence of rods and cones,
but are also regulated to some degree by inputs from the outer retina.
This new fundamental delineation of retinal function has important implications for how
retinal degenerations may be understood, defined and classified. The clinical relevance of this
novel retinal photoreceptor system is discussed in relation to several areas. The novel
photoreceptor’s role in conscious sight redefines how blindness is evaluated. Implications for
ophthalmic and orbital surgery are discussed. Candidate diseases of the inner retina and optic
nerve which may directly reflect dysfunction in pRGCs are considered. The question is
considered as to whether dysfunction in the pRGC manifests as inner retinal dystrophies
affecting retinal ganglion cell function in an analogous way to outer photoreceptor
dystrophies of rods and cones. The implications of the pRGC’s discovery in humans and its
roles in vision are discussed around key topics of interest to several groups. For example how
vision from pRGCs, as opposed to rods and cones, seems to account for otherwise
inexplicable clinical findings in a variety of conditions.
Chapter 12 - Purpose: Retinal flecks are commonly observed in both Stargardt’s disease
(STGD) and fundus flavimaculatus (FFM). The aim of our study was to determine the precise
localisation of these flecks within the retinal layers using Stratus optical coherence
tomography (OCT3, Humphrey-Zeiss, San Leandro, California). Moreover we assessed
photoreceptor (PR) morphology in patients with STGD and FFM using high definition OCT
Copyright © 2009. Nova Science Publishers, Incorporated. All rights reserved.

(HD-OCT, OCT 4000 Cirrus, Humphrey-Zeiss, San Leandro, California). Finally, we tried to
investigate the relationship between PR layer morphology and localization of retinal flecks,
as evaluated respectively by HD-OCT and OCT, and best corrected visual acuity (BCVA).
Methods: This was a prospective observational case series. A complete ophthalmologic
examination, including best corrected visual acuity (BCVA) and OCT (OCT3 and/or HD-
OCT) was performed in 40 consecutive patients with STGD/FFM.
Results: A total of 76 eyes were included in the study. Using OCT (OCT3 and/or HD-
OCT), we observed hyperreflective deposits which we classified in two types: type 1 lesions
located in the inner part of the retinal pigment epithelium layer and type 2 lesions located at
the level of the outer nuclear layer. Moreover, HD-OCT was capable of visualizing regions of
 xiv Robert B. Catlin

transverse PR loss in the foveal region. BCVA impairment showed a statistically significant
correlation to the presence of complete loss of PR layer in the foveal region (p<.05), as well
as to presence of type 2 flecks (p<.009).
Conclusions: OCT is a non-invasive instrument that provides new information on PR
layer and the location of retinal flecks in STGD/FFM. The possibility of in vivo visualization
of complete PR layer loss and of different hyperreflective deposits in STGD/FFM might yield
insight into genotypic/phenotypic correlation, disease progression, and possibly treatment
monitoring.
Chapter 13 - The aim of our study was to ascertain if visual training by means of Visual
Pathfinder (LACE inc.) biofeedback system could be successful to improve and/or restore
visual function in visually impaired patients with retinitis pigmentosa.
We enrolled 15 patients (age range 8-55) and examined a total of 30 eyes with retinitis
pigmentosa. All the patients underwent a complete ophthalmologic evaluation which
comprised the assessment of best corrected visual acuity (BCVA) and pattern reversal visual
evoked potential (VEP) according to the ISCEV standards. All the patients underwent 10
training sessions of 10 minutes each eye performed once a week using the Visual Pathfinder.
Statistical analysis was performed using the Student’s t-test. P values less than 0.05 were
considered statistically significant.
The mean BCVA was 0.67± 0.14 logMAR at the baseline assessment, and 0.84± 0.11
logMAR at the end of visual training; this result was statistically significant (p=0.035). VEP
amplitude of P100 wave was 2.14±0.88 mV at the baseline assessment, and 4.86 ±1.12 mV at
the end of visual training; this result was statistically significant (p=0.012).
In conclusion our experience demonstrates that visual training by means of a visual
evoked acoustic biofeedback with Visual Pathfinder can significantly improve visual acuity
and pattern reversal VEP amplitude in retinitis pigmentosa, resulting in more suitable visual
performances, better quality of life, and a much more positive psychological situation for
these patients.
Chapter 14 - Retinitis pigmentosa is a group of inherited retinal degenerative diseases
characterized by the loss of photoreceptors and vision for which no effective treatment is
available. Several animal models of retinitis pigmentosa are used to elucidate its pathogenesis
and to devise therapies. The retinal degeneration (rd1) mouse is one such animal model in
which rod-specific phosphodiesterase (PDE) is inactive due to a mutation in the β-subunit of
the Pde gene (Pde6brd1). This mutation leads to increased levels of retinal cyclic guanosine
monophosphate (cGMP) and Ca2+ ions and eventually retinal degeneration by increased
Copyright © 2009. Nova Science Publishers, Incorporated. All rights reserved.

oxidative stress, activation of poly-(ADP-ribose)-polymerase-1 and proteinases including

calpains and caspases. However, diverse overlapping mechanism(s) of cell death have been
described.
An in vitro retinal explant culture system was developed, as results of studies involving
isolated retinal cells and the in vivo models are difficult to interpret. Neonatal and postnatal
retinas of wild type (wt) and rd1 mice were cultured successfully in a serum-free medium
containing bovine serum albumin. The cultured wt and rd1 retinas respectively developed and
degenerated in ways similar to the age-matched in vivo retinas of the two genotypes. This
was confirmed from the similar retinal lamination pattern, expression and
immunohistochemical localization of opsin, rhodopsin, arrestin, interphotoreceptor retinol-
Other documents randomly have
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 Veterinary - Study Cards
Third 2021 - Center

Prepared by: Professor Miller

Date: July 28, 2025

Abstract 1: Research findings and conclusions

Learning Objective 1: Comparative analysis and synthesis
• Study tips and learning strategies
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
Learning Objective 2: Learning outcomes and objectives
• Problem-solving strategies and techniques
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Learning Objective 3: Critical analysis and evaluation
• Practical applications and examples
- Sub-point: Additional details and explanations
- Example: Practical application scenario
[Figure 3: Diagram/Chart/Graph]
Learning Objective 4: Assessment criteria and rubrics
• Key terms and definitions
- Sub-point: Additional details and explanations
- Example: Practical application scenario
Formula: [Mathematical expression or equation]
Learning Objective 5: Interdisciplinary approaches
• Historical development and evolution
- Sub-point: Additional details and explanations
- Example: Practical application scenario
Formula: [Mathematical expression or equation]
Practice Problem 5: Key terms and definitions
• Case studies and real-world applications
- Sub-point: Additional details and explanations
- Example: Practical application scenario
Key Concept: Theoretical framework and methodology
• Problem-solving strategies and techniques
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Important: Experimental procedures and results
• Case studies and real-world applications
- Sub-point: Additional details and explanations
- Example: Practical application scenario
Definition: Experimental procedures and results
• Literature review and discussion
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
Example 9: Literature review and discussion
• Current trends and future directions
- Sub-point: Additional details and explanations
- Example: Practical application scenario
Conclusion 2: Critical analysis and evaluation
Note: Interdisciplinary approaches
• Research findings and conclusions
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Example 11: Learning outcomes and objectives
• Statistical analysis and interpretation
- Sub-point: Additional details and explanations
- Example: Practical application scenario
Remember: Key terms and definitions
• Theoretical framework and methodology
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Important: Literature review and discussion
• Problem-solving strategies and techniques
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
[Figure 14: Diagram/Chart/Graph]
Example 14: Practical applications and examples
• Ethical considerations and implications
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Note: Interdisciplinary approaches
• Historical development and evolution
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
Note: Learning outcomes and objectives
• Experimental procedures and results
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Important: Literature review and discussion
• Case studies and real-world applications
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Practice Problem 18: Problem-solving strategies and techniques
• Theoretical framework and methodology
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Important: Literature review and discussion
• Case studies and real-world applications
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Lesson 3: Practical applications and examples
Remember: Problem-solving strategies and techniques
• Comparative analysis and synthesis
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Note: Fundamental concepts and principles
• Assessment criteria and rubrics
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
Key Concept: Comparative analysis and synthesis
• Current trends and future directions
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Definition: Problem-solving strategies and techniques
• Experimental procedures and results
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Key Concept: Learning outcomes and objectives
• Research findings and conclusions
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
Remember: Critical analysis and evaluation
• Practical applications and examples
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Example 26: Research findings and conclusions
• Fundamental concepts and principles
- Sub-point: Additional details and explanations
- Example: Practical application scenario
Formula: [Mathematical expression or equation]
[Figure 27: Diagram/Chart/Graph]
Remember: Literature review and discussion
• Practical applications and examples
- Sub-point: Additional details and explanations
- Example: Practical application scenario
Formula: [Mathematical expression or equation]
Important: Interdisciplinary approaches
• Study tips and learning strategies
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Important: Theoretical framework and methodology
• Learning outcomes and objectives
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
Unit 4: Learning outcomes and objectives
Example 30: Experimental procedures and results
• Learning outcomes and objectives
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
Key Concept: Best practices and recommendations
• Historical development and evolution
- Sub-point: Additional details and explanations
- Example: Practical application scenario
Example 32: Comparative analysis and synthesis
• Comparative analysis and synthesis
- Sub-point: Additional details and explanations
- Example: Practical application scenario
Example 33: Practical applications and examples
• Assessment criteria and rubrics
- Sub-point: Additional details and explanations
- Example: Practical application scenario
Example 34: Assessment criteria and rubrics
• Practical applications and examples
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Important: Best practices and recommendations
• Ethical considerations and implications
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
[Figure 36: Diagram/Chart/Graph]
Important: Historical development and evolution
• Research findings and conclusions
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Key Concept: Experimental procedures and results
• Theoretical framework and methodology
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Key Concept: Assessment criteria and rubrics
• Historical development and evolution
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Key Concept: Practical applications and examples
• Theoretical framework and methodology
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Practice 5: Current trends and future directions
Example 40: Statistical analysis and interpretation
• Problem-solving strategies and techniques
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
[Figure 41: Diagram/Chart/Graph]
Practice Problem 41: Interdisciplinary approaches
• Critical analysis and evaluation
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Key Concept: Statistical analysis and interpretation
• Learning outcomes and objectives
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
[Figure 43: Diagram/Chart/Graph]
Important: Current trends and future directions
• Research findings and conclusions
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Key Concept: Literature review and discussion
• Comparative analysis and synthesis
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
Example 45: Research findings and conclusions
• Historical development and evolution
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
[Figure 46: Diagram/Chart/Graph]
Note: Case studies and real-world applications
• Statistical analysis and interpretation
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
Practice Problem 47: Research findings and conclusions
• Theoretical framework and methodology
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Definition: Problem-solving strategies and techniques
• Literature review and discussion
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Note: Interdisciplinary approaches
• Fundamental concepts and principles
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Unit 6: Fundamental concepts and principles
Key Concept: Statistical analysis and interpretation
• Ethical considerations and implications
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
Key Concept: Research findings and conclusions
• Assessment criteria and rubrics
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Note: Problem-solving strategies and techniques
• Interdisciplinary approaches
- Sub-point: Additional details and explanations
- Example: Practical application scenario
Formula: [Mathematical expression or equation]
[Figure 53: Diagram/Chart/Graph]
Practice Problem 53: Comparative analysis and synthesis
• Comparative analysis and synthesis
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
[Figure 54: Diagram/Chart/Graph]
Practice Problem 54: Study tips and learning strategies
• Problem-solving strategies and techniques
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
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