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   Table of Contents      
OPHTHALMOLOGY PRACTICE
Year : 2003  |  Volume : 51  |  Issue : 1  |  Page : 89-97

Programme planning and screening strategy in retinopathy of prematurity.


Smt. Kannuri Santhamma Retina-vitreous centre, L V Prasad Eye Institute, Banjara Hills, Hyderabad, India

Correspondence Address:
S Jalali
Smt. Kannuri Santhamma Retina-vitreous centre, L V Prasad Eye Institute, Banjara Hills, Hyderabad
India
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Source of Support: None, Conflict of Interest: None


PMID: 12701873

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  Abstract 

Retinopathy of Prematurity (ROP) is one of the major emerging causes of childhood blindness. A well organised screening strategy and timely intervention can to a large extent prevent blindness due to ROP. This communication proposes a screening strategy and management plan to develop a model for the care of babies with ROP.

Keywords: Retinopathy of prematurity, screening, training


How to cite this article:
Jalali S, Anand R, Kumar H, Dogra MR, Azad R, Gopal L. Programme planning and screening strategy in retinopathy of prematurity. Indian J Ophthalmol 2003;51:89-97

How to cite this URL:
Jalali S, Anand R, Kumar H, Dogra MR, Azad R, Gopal L. Programme planning and screening strategy in retinopathy of prematurity. Indian J Ophthalmol [serial online] 2003 [cited 2019 Dec 14];51:89-97. Available from: http://www.ijo.in/text.asp?2003/51/1/89/14727



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Over the past decade, our understanding of the pathogenesis of Retinopathy of Prematurity (ROP) has improved tremendously. Extensive clinical trials and publications[1],[2],[3],[4] have established that among other factors gestation period and low birth weight are critical in the pathophysiology of ROP. If detected early and treated with peripheral retinal cryopexy or laser, ROP blindness can be prevented to some extent. [4],[5],[6],[7] Beyond this stage, very few eyes can be saved even by extensive vitreoretinal surgery.[8],[9],[10] Thus there is a need to train ophthalmologists and other health care personnel in the screening and management of ROP.


  The magnitude Top


The reported incidence of ROP in the West ranges from 21 to 65.8%.[2],[11] In infants weighing less than 900 grams at birth and with a gestational age of less than 25 weeks, the incidence is as high as 80-100%.[1],[12] Recent Indian studies have shown that the incidence of ROP varies from 38-51.9% among low birth-weight babies.[13],[14],[15] Newborn infants with birth weight less than 1500 grams and gestational age below 34 weeks constitute about 1.9% of the total live births in a tertiary level neonatal care unit in India.[15] With the increasing number of neonatal care units across the country the total number of infants requiring screening and treatment for ROP is certain to increase. In the absence of an effective screening strategy an increasing number of premature infants who could have been successfully managed may turn irreversibly blind. The social and economic burden for such childhood blindness is immense.


  The screening Top


Why should we screen for ROP?

There are several compelling reasons to have a screening programme for ROP.[16] Firstly, the premature child is not born with ROP and retinal disease is not present at birth. Each such child has a potential for normal vision, even if the retina is immature at birth. Screening aims to identify those infants who have reached or have the potential to reach threshold ROP, which if untreated may cause blindness or visual impairment. This has medico-legal implications. There are indefensible legal repercussions should an infant develop ROP and retinal detachment, but had not received eye examination. Secondly, the grief and the personal tragedy for the family is tremendous, besides the economic burden of such childhood blindness. Early recognition of ROP by screening[16] provides an opportunity for effective treatment.

How can we start a screening programme in an NICU?

Where no such programme exists, one should begin by educating fellow physicians/neonatologists and nursing staff, using relevant scientific literature to highlight the ROP management issues. One of the key factors in establishing and maintaining a successful programme is to convince the administrative body, the physicians, paediatricians and nursing staff of the neonatal intensive care unit (NICU) about the necessity and effectiveness of the programme.

A responsible person in the nursery should be designated to coordinate the selection of the 'at risk' infants according to the guidelines of the ophthalmologist and ensure their eye evaluation at the appropriate time. An airtight system should be decided for initial evaluation as well as for follow-up visits so as to avoid any eligible infant falling out of this net. The moral and legal responsibility of getting the baby to the ophthalmologist for screening at the appropriate time rests solely with the paediatrician. Written guidelines and criteria for ROP screening provided to the NICU staff by the ophthalmologist [Table - 1][Table - 2] help streamline the programme.

Once the programme is accepted, a trained ophthalmologist is needed to conduct the eye examination. This could be a paediatric ophthalmologist, a retina specialist or a general ophthalmologist who has the interest and flair to examine neonates and who is available consistently. A short hands-on course could be useful for those unfamiliar with this disease.

Whom should we screen?

The aim of screening premature babies for ROP is to detect all treatable neonates, with minimal expense of time and resources. This also aims at not screening those babies who are unlikely to get a severe form of ROP. The criteria for screening babies are based on two critical factors - the birth weight and the gestational age. Other additional factors contributing to the development of ROP are also taken into consideration [Table - 1].

Although much has been written about the association of oxygen use and ROP, it has been found that oxygen is not the cause of ROP. [3] On the contrary, low levels of oxygen and slow weaning from oxygen may help regression of early stages of ROP.[3] Oxygen levels must be well monitored to ensure optimum oxygen saturation of blood (95-98%), since hypoxia is a factor in increasing abnormal retinal neovascularisation.

When should screening begin?

A premature infant is not born with ROP. The retina is immature, but this is perfectly natural for their age. It is the post-natal developments in the retinal vessels that could lead to ROP. The sequence of events leading to ROP usually takes about 4-5 weeks except in a small subset of premature infants who develop Rush disease in 2-3 weeks. Therefore routine screening should begin at no later than four weeks after the birth and possibly even earlier for infants at higher risk (2-3 weeks)[4],[16] [Table - 2]. We strongly recommend that one session of retinal screening be carried out before day 30 of the life of any premature baby.

How frequently should we examine?

The ophthalmologist plans for further follow-up examinations based on the initial fundus findings [Table - 3]. The following schedule could be used as a guideline.

1. Further evaluation for ROP is not needed if the retina is fully mature (defined as retinal vessels seen up to nasal ora serrata, in the context of ROP). This usually occurs by 40 weeks post-conceptional age.[17] These babies, however, need to see an ophthalmologist for refraction, vision assessment, and ocular alignment (squint) at 3-12 months of age. Preterm babies are at higher risk for developing ammetropia, delayed visual maturation and squint.[18] If there is no apparent squint or vision problem, the child can be seen at one year of age. If there is an obvious squint, nystagmus, tearing, discharge, photophobia, leucocoria or vision loss, then early evaluation is needed. Usually the eyes are well aligned, and have good ability to fixate and follow an object by three months of age.

2. If the retina is immature (retinal vessels are not seen up to nasal ora serrata) then baby must be screened every two weeks till the retina is mature.

3. In eyes with retinal vessels seen only up to the Zone I area at initial visit, weekly evaluation is needed. These eyes can develop fulminate ROP or Rush disease very quickly, and not necessarily the classical stages 1-3 before reaching threshold ROP.

4. If there are early signs of ROP then the child must be examined every week for any progression or regression of the disease.

5. If child develops pre-threshold ROP, then the child should be seen every 3-7 days for progression.

6. In case of threshold ROP, urgent peripheral retinal laser/ cryo ablation should be done within 48-72 hours.

7. In eyes with ROP stage 4 or 5, early surgical treatment such as belt buckling or vitreous surgery[19] can help save some vision, though the majority have a dismal prognosis.

8. In case of any doubt about the retinal findings (especially by beginners) it is a good practice to examine the baby again every 1-2 weeks, at least till the child is 38-40 weeks old.

How do we dilate?

The recommended eye drops are tropicamide 0.5% - 1% with phenylepherine 2.5%. Two to three instillations of each of these drops, five minutes apart are usually sufficient to dilate the pupils in 15-20 minutes; and the effect remains for 30-45 minutes. Cyclopentolate 0.5% to 1.0% can also be used safely. Care should be taken to wipe (with sterile cotton/tissue) any eye drops that spills onto the cheeks, as they can be absorbed from the skin of the babies and cause increased heart rate. It is not advisable to use 10% phenylepherine or atropine (drops or ointment) in premature babies for screening, as severe tachycardia, and fatal hyperthermia and dehydration can occur due to systemic absorption. Use of any dilating eye drops (or even antibiotic or corticosteroid eye drops) in premature babies can be life threatening and should not be taken casually.

[ Note: In India only 10% (and sometimes 5%) phenylepherine is available commercially. A 10% solution needs dilution in 1:4 ratio. To prepare 2.5% solution, dilution can be done with methylcellulose eye drops or commercially available distilled water.]

Where should the examination be done?

When preparing the screening away from one's own office, the ophthalmologist should ensure from a checklist [Table - 4] that all instruments/forms needed are packed. The place of screening must be warm and clean enough for the baby. This is often the nursery/ office of the neonatologist but can also be the office of the ophthalmologist. The baby should be well clothed and wrapped; and the baby should be preferably fed and burped an hour before evaluation. Babies who are critically ill or in NICU are evaluated in the NICU/ incubator under the guidance of the neonatologist, monitored by a pulse oxymeter. As soon as the baby arrives for screening, a quick flashlight evaluation of adnexa and anterior segment (to rule out any congenital ocular anomaly) is done before instilling the dilating drops. While awaiting dilatation over the next 10-15 minutes, all the data about the baby are obtained. At the end of the evaluation, rest of the forms/diagrams are completed and discussion with the parents/paediatrician/staff about the retinal status carried out. Alternatively, if only a couple of babies need be screened, the staff can be asked to dilate 15-20 minutes before arrival of the examiner. One should always remember that errors in dilution of dilating drops can prove fatal for the baby.


  The Examination13-15 Top


Proficiency in using indirect ophthalmoscope is mandatory. A condensing lens of 20D or 28 D/ 30D may be used for this purpose. The advantage of using 28D/30D is its wider area of view, though the magnification is less. In case of Plus disease a 20 D lens is advocated for comparison with the standard photograph provided by CRYO-ROP study.[4],[16] An infantile speculum may be used to keep the eye open or the examiners may open it with their fingers. Oculocephalic reflex, wherein the head of baby is turned towards the side to be evaluated, can be used to examine the peripheral retina. Scleral depression with either a simple wire vectis or specially designed commercially available neonatal scleral depressor may be needed in only few cases. Examination for ROP does not require any sedation or general or even topical anaesthesia.

The anterior segment is first examined with the condensing lens focussed on the cornea, iris, pupil and lens to look for any media opacity, tunicosa vasculosa lentis or dilated tortuous iris new vessels. Ease and extent of pupillary dilatation is noted. Next, retinal evaluation is done starting with evaluation of media clarity. The posterior pole over the area of Zone I is examined for disc, macula and retinal vessels. Any evidence of Plus disease, vascular loops or retinal avascularity is ruled out. Area of zone II can be examined by using little sideways movement of the head. First the nasal periphery should be examined till the ora serrata. Any evidence of immaturity or ROP in the nasal periphery would qualify the disease for Zone II. Complete vascularisation of the nasal periphery with the avascular area in the temporal periphery would qualify the disease for Zone III. Findings of the examination are noted using standard protocols ( vide infra ).


  Classification Top


All the findings of the examination must be well documented according to the international classification for retinopathy of prematurity (ICROP)[20] recommenda-tions specifying the location (Zone I-III) and severity of the disease (Stage I-V), with or without Plus component and the extent of clock hours.

Location of the disease (Zones)

The normal blood vessels of the retina progress from the optic nerve posteriorly to the edge of the retina (ora serrata) anteriorly.[17],[20] The location of ROP is a measure of how far this normal progression of blood vessel development has reached before the disease takes over. Three circular zones are defined with the optic disc at the centre [Figure - 1].

Zone I is a small area around the optic nerve and macula. The radius of Zone I is equal to twice the distance between the disc and the fovea. Disease in Zone I is the most dangerous.

Zone II is up to the equator on the temporal side and up to the ora serrata on the nasal side.

Zone III is the remaining crescent of retina from the equator to the ora on the temporal side.


Extent of the disease (clock hours)

The eye is divided into twelve sectors similar to a clock. The extent of ROP is defined by how many clock hours of the eye's circumference is diseased. The extent can vary from 1 to 12 clock hours [Figure - 1].

Plus disease

Any stage or zone of ROP may be associated with additional component of Plus Disease . Plus disease is characterised by abnormal dilated vessels on the iris [Figure - 2] and/or engorgement and tortuosity of the blood vessels in the retina [Figure - 3]. Additional findings include retinal haemorrhages, poorly dilating pupil and hazy media.

Stages of the disease (severity)

ROP is a progressive disease. It starts slowly, usually anywhere from the third to the tenth week of life and may progress very fast or very slowly through successive stages, from stage 1 through 5. It may cease at stage 1, stage 2, or mild stage 3 and finally disappear completely, without affecting vision.

Stage 1 ROP is characterised by a white line separating the clearly normal red/ pink retina from the sharply contrasting underdeveloped white/grey retina [Figure - 4].

Stage 2 ROP displays a rolled ridge of scar tissue instead of only a line. It may be limited to a small area [Figure - 5], full arrow or encircle the entire inside of the eye like a belt, around the middle of the eye.

Stage 3 ROP is characterised by the development of abnormal new blood vessels and fibrous, scar tissue [Figure - 5], arrowhead on the edge of the ridge seen in stage 2. These vessels are lifted off from the surface and project into the vitreous cavity. Since more than 50% eyes with stage 3 will progress to stage 4 or 5, treatment with laser or cryopexy is considered in this stage.

Stage 4 ROP occurs due to pulling of the retina by the scar tissue so that the retina separates from the wall of the eyeball. In stage 4 the retinal detachment (RD) is partial, involving only some part of the retina. Depending on the extent of RD stage 4 is further divided into stage 4A (sparing macula) and 4B (involving macula).

In stage 4 A , the eyes have reasonably good chance of achieving usable vision should the retina be reattached. In stage 4 B, the partial RD involves the macula, usually with a fold extending from the optic disc through Zones I, II and III. The involvement of the macula severely limits the prospect of usable vision in such eyes. In stages 4A and 4B, surgery at the earliest may help to salvage some useful vision.[19]

Stage 5 ROP involves complete retinal detachment [Figure - 6], with the retina assuming a partial or closed funnel configuration. The infant usually develops a white reflex in the eye (leukocoria) which can sometimes be mistaken as a cataract [Figure - 7]. Infants with stage 5 ROP have essentially no useful vision in the affected eye. Treatment at this stage involves surgery to reattach the retina. Some vision may be recovered after this surgery but usually the eye becomes legally blind. [8],[10]

Rush disease

Rush disease is Zone I ROP with signs of Plus disease. In Rush disease progression of ROP is rapid and fulminant. Any stage of ROP in Zone I needs very close monitoring and early treatment if it shows progression. One needs to look for close-end vascular loops at the end of the arcades [Figure - 8] and particularly in the nasal peripapillary area. New vessels that are initially flat and in groups and later get elevated to extend into the vitreous cavity may rapidly progress in the nasal retina. This type of disease is also called Posterior Zone I / Fulminate ROP / Type II ROP . This can be quite difficult to diagnose and treat. It often occurs in the smallest babies. Failures of treatment are highest in this group and hence such eyes need vigorous and early treatment.

Pre-threshold ROP

This is defined as ROP in Zone I, any stage; Zone II with stage 2 and Plus component; Zone III or Zone II with stage 3 and Plus component but not reaching threshold clock hours. If ROP is in the pre-threshold stage it requires very close observation as it can rapidly progress to threshold, which needs prompt treatment.

Threshold ROP

This is defined as Zone 1 or Zone 2 with stage 3+ ROP extending for 5 contiguous sectors or 8 composite sectors. This stage needs laser or cryotherapy in less than 72 hours [Figure - 9].

Recording of findings at ROP screening


The retinal examination findings are recorded using universally acceptable graphical representation and standard notation [Figure - 1][Figure - 10] from the CRYO-ROP[20] and STOP-ROP studies.[3] The findings should be recorded in appropriate forms (Appendix I) so as not to miss any critical information.


  Treatment Top


ROP is essentially a disease of prevention. If ROP is detected in the prethreshold or early threshold stage it responds well to treatment. Both cryotherapy and laser photocoagulation are effective.[4],[5],[6],[7] Each of these has its own advantages and disadvantages. The main advantage of laser is the ability to apply it either without anaesthesia or under topical anaesthesia. Cryopexy usually demands general anaesthesia, though general anaesthesia in this group of patients carries significant morbidity. The complete avascular area of the retina is ablated in the treatment to decrease the hypoxic drive and therefore stimulus for progression of the disease. The treatment methodology is beyond the scope of the present article.


  Training of Personnel Top


General ophthalmologist (primary care)

General ophthalmologists could be trained to identify babies at risk in their locality. They would also be able to build a liaison with paediatricians/ neonatologists in their area so that infants at risk may be referred for screening to the closest trained retina surgeon. The essential requirement for this is expertise in indirect ophthalmoscopy. Direct ophthalmoscopy can detect most of the eyes with vision-threatening Plus disease but will miss the peripheral retinal changes of ROP.

Retina surgeon (secondary care)

A trained retina surgeon should be able to screen and treat the easily treatable stages of the disease. Those infants presenting late or requiring surgery should be referred to a tertiary center.

ROP surgeon (tertiary care)

Candidates must be experienced in modern vitreoretinal surgery. Training should be at the highest level in the tertiary center, as such surgeons would be dealing with the most difficult cases of ROP.

Neonatologist / Paediatrician

They should be trained to identify neonates at risk of developing ROP and refer to the ophthalmologist whenever needed. They should also be able to educate the parents of newborns about the importance of eye examination and timely treatment for babies at risk.

Other personnel

Nurses working in the neonatal care unit should be educated to understand and communicate to the parents the advantages of the ROP screening program. Awareness in the general public, especially among parents of newborns, may be increased with posters and information pamphlets distributed in and around the neonatal care area.


  Longterm Vision Concerns in Premature Infants Top


Premature children have a greater chance of developing refractive errors such as high myopia, myopic astigmatism, anisometropic amblyopia and strabismus.[4],[5],[18] These conditions can occur in premature children with or without ROP. Additional problems, specifically in eyes treated for ROP, include cataract, glaucoma and late onset retinal detachment or vitreous haemorrhage. Hence, children treated for ROP need life-long periodic eye examinations. In first few years, examinations are done under anaesthesia for proper refraction and intraocular pressure measurements. Premature babies can also have delayed visual maturation and apparent inability to see and recognise (often misdiagnosed as optic atrophy or blindness), due to cerebral palsy and other central nervous system disorders. These patients need detailed evaluation for presence or absence of ocular pathology. Many of these babies will see normally as the visual cortical systems mature, but all of them need repeated evaluations.

Babies treated successfully or unsuccessfully for ROP Stage 4B and beyond need extensive vision training and visual rehabilitation measures (including low vision aids) to utilise the residual vision to its maximum potential. This vision training is an essential part of any good ROP treatment program. Further information on ROP is available on the ROP website at

The incidence of ROP is increasing in India due to improved neonatal facilities. Fortunately, the disease course in ROP offers a unique opportunity for the physician to identify and treat the disease. Most premature babies at risk of developing the disease are already under the care of physician, so one does not need to go into the community to screen for this disease. One needs to organise a network among the fellow physicians, paramedical staff and parents, for early detection and effective treatment of ROP. With a proper screening and management strategy [Figure - 11] we should succeed in decreasing visual loss due to the retinopathy of prematurity.

 
  References Top

1.
Palmer EA, Flynn JT, Hardy RJ, Phleps DL, Phillips CL, Schaffer DB. Incidence and early course of retinopathy of prematurity. Ophthalmology 1991;98:1628-40.  Back to cited text no. 1
    
2.
Fielder AR, Shaw DF, Robinson J, Ng YK. Natural history of retinopathy of prematurity: A prospective study. Eye 1992;6:233-42.  Back to cited text no. 2
    
3.
STOP-ROP Multicentre Study Group. Supplemental therapeutic oxygen for prethreshold retinopathy of prematurity (STOP-ROP), a randomised controlled trial: Primary outcomes. Pediatrics 2000;150:295-10.  Back to cited text no. 3
    
4.
Cryotherapy for Retinopathy of Prematurity Cooperative Group. Multicenter trial of cryotherapy for retinopathy of prematurity-Three-month outcome. Arch Ophthalmol 1990;108:195-40.  Back to cited text no. 4
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Cryotherapy for Retinopathy of Prematurity Cooperative Group. Multicenter trial of cryotherapy for retinopathy of prematurity-3Z\x years outcome for both structure and function. Arch Ophthalmol 1993;111:339-44.  Back to cited text no. 5
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Tsisis T, Tasman W, Mcnamara JA, Brown G, Vander J. Diode laser photocoagulation for retinopathy of prematurity. Trans Am Ophthal Soc 1997;95:231-36.  Back to cited text no. 6
    
7.
Despande DA, Chaturvedi M, Gopal L, Ramachandram S, Shanmugasundaram R. Treatment of threshold retinopathy of prematurity. Indian J Ophthalmol 1998;46:15-19.  Back to cited text no. 7
    
8.
Cherry TA, Lambert SR, Capone-A Jr. Electroretinographic findings in stage V retinopathy of prematurity after retinal reattachment. Retina 1995;15:21-24.  Back to cited text no. 8
    
9.
Noorily SW, Small K, Juan E de, Machemar R. Scleral bucking surgery for stage 4B retinopathy of prematurity. Ophthalmology 1992;99:263-68.   Back to cited text no. 9
    
10.
Gopal L, Sharma T, Shanmugam M, Badrinath SS, Sharma A, Agraharam SG, et al. Surgery for stage 5 ROP-the learning curve and evolving techniques. Indian J Ophthalmol 2000;48;101-106.  Back to cited text no. 10
    
11.
Darlow BA. Incidence of retinopathy of prematurity in New Zealand. Arch Dis in Childhood 1998;63:1083-86.  Back to cited text no. 11
    
12.
Coats DK, Paysse EA, Steinkuller PG. Threshold retinopathy of prematurity in neonates less than 25 weeks estimated gestational age. J Am Asso Pediatr- Ophthathalmol-Strabisbus 2000;4:183-85.  Back to cited text no. 12
    
13.
Gopal L, Sharma T, Ramchandran S, Shanmugasundaram R, Asha V. Retinopathy of prematurity. A study. Indian J Ophthalmol 1995;43:50-61.  Back to cited text no. 13
    
14.
Charan R, Dogra MR, Gupta A, Narang A. The incidence of retinopathy of prematurity in a neonatal care unit. Indian J Ophthalmol 1995;43:123-26.  Back to cited text no. 14
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Varughese S, Jain S, Gupta N, Singh S, Tyagi V, Puliyel JM. Magnitude of the problem of retinopathy of permaturity. Experience in a large maternity unit with a medium size level-3 nursery. Indian J Ophthalmol 2001:49:187-88.   Back to cited text no. 15
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16.
Kumar H, Shapiro MJ: ROP screening examination guidelines and methodology. In: Kumar H, Shapiro MJ, Azad RV, editors. A Practical Approach to Retinopathy of Prematurity Screening and Management. New Delhi. Malhotra Enterprises, 2001. pp 45-57.  Back to cited text no. 16
    
17.
Roth AM. Retinal vascular development in premature infants. Am J Ophthalmol 1977;84:636-41.  Back to cited text no. 17
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18.
Choi MY, Park IK, Yu YS. Long term refractive outcome in eyes of preterm infant with and without retinopathy of prematurity: comparison of keratometric values, axial length and anterior chamber depth and lens thickness. Br J Ophthalmol 2000;84:138-43.  Back to cited text no. 18
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19.
Trese MT, Droste PJ. Long-term postoperative results of a consecutive series of stages 4 and 5 retinopathy of prematurity. Ophthalmology 1998;105:992-97.  Back to cited text no. 19
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    Figures

  [Figure - 1], [Figure - 2], [Figure - 3], [Figure - 4], [Figure - 5], [Figure - 6], [Figure - 7], [Figure - 8], [Figure - 9], [Figure - 10], [Figure - 11]
 
 
    Tables

  [Table - 1], [Table - 2], [Table - 3], [Table - 4]


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