Retinopathy of Prematurity

Overview

Epidemiology

• Retinopathy Retinopathy Degenerative changes to the retina due to hypertension. Alport Syndrome of prematurity Prematurity Neonatal Respiratory Distress Syndrome is the leading cause of blindness in infants.
• The incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency of the disease is inversely proportional to:
  • Gestational age Gestational age The age of the conceptus, beginning from the time of fertilization. In clinical obstetrics, the gestational age is often estimated as the time from the last day of the last menstruation which is about 2 weeks before ovulation and fertilization. Pregnancy: Diagnosis, Physiology, and Care of the patient
  • Birth weight

Risk factors

• Low birth weight
• Low gestational age Gestational age The age of the conceptus, beginning from the time of fertilization. In clinical obstetrics, the gestational age is often estimated as the time from the last day of the last menstruation which is about 2 weeks before ovulation and fertilization. Pregnancy: Diagnosis, Physiology, and Care
• Supplemental oxygen Supplemental Oxygen Respiratory Failure therapy
• Genetic predisposition
• Infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease
• Congenital Congenital Chorioretinitis cardiac defects

Pathophysiology

Premature Premature Childbirth before 37 weeks of pregnancy (259 days from the first day of the mother’s last menstrual period, or 245 days after fertilization). Necrotizing Enterocolitis infants of low birth weight are at risk of developing hyperoxia during their care; this can lead to:

• Reactive oxygen species Reactive oxygen species Molecules or ions formed by the incomplete one-electron reduction of oxygen. These reactive oxygen intermediates include singlet oxygen; superoxides; peroxides; hydroxyl radical; and hypochlorous acid. They contribute to the microbicidal activity of phagocytes, regulation of signal transduction and gene expression, and the oxidative damage to nucleic acids; proteins; and lipids. Nonalcoholic Fatty Liver Disease production → causing damage to the retina Retina The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outermost layer is pigmented, whereas the inner nine layers are transparent. Eye: Anatomy
• Abnormal vascular endothelial growth factor Vascular endothelial growth factor A family of angiogenic proteins that are closely-related to vascular endothelial growth factor a. They play an important role in the growth and differentiation of vascular as well as lymphatic endothelial cells. Wound Healing (VEGF) production → causing abnormal neovascularization
• Newly formed vessels are different than normal ones:
  • Abnormally permeable
  • Grow outside retina Retina The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outermost layer is pigmented, whereas the inner nine layers are transparent. Eye: Anatomy
• Development of abnormal fibrovascular tissue occurs and pulls the retina Retina The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outermost layer is pigmented, whereas the inner nine layers are transparent. Eye: Anatomy, causing retinal detachment Retinal detachment Retinal detachment is the separation of the neurosensory retina from the retinal pigmented epithelium and choroid. Rhegmatogenous retinal detachment, the most common type, stems from a break in the retina, allowing fluid to accumulate in the subretinal space. Retinal Detachment.

Classification

International classification of retinopathy Retinopathy Degenerative changes to the retina due to hypertension. Alport Syndrome uses a number of parameters to describe the disease:

• Defining which “zone” is involved
• Defining the “extent” of retinal involvement (expressed as segments on a clock)
• Defining the severity of disease, or “stage” (see table below)
• The presence or absence of  “plus disease” (e.g., venous dilation and arterial tortuosity of the posterior retinal vessels)

Screening

Indication to screen

• All infants of low birth weight (< 1,500 g)
• All infants born before 30 weeks‘ gestational age Gestational age The age of the conceptus, beginning from the time of fertilization. In clinical obstetrics, the gestational age is often estimated as the time from the last day of the last menstruation which is about 2 weeks before ovulation and fertilization. Pregnancy: Diagnosis, Physiology, and Care
• Infants between 1,500 g and 2,000 g birth weight and born after 30 weeks’ gestation who are exposed to potential risk factors (see above)

Screening Screening Preoperative Care methods

• When to screen:
  • For infants born between 22 and 26 weeks, when they reach 30 weeks’ corrected gestational age Gestational age The age of the conceptus, beginning from the time of fertilization. In clinical obstetrics, the gestational age is often estimated as the time from the last day of the last menstruation which is about 2 weeks before ovulation and fertilization. Pregnancy: Diagnosis, Physiology, and Care
  • For infants ≥ 27 weeks’ gestational age Gestational age The age of the conceptus, beginning from the time of fertilization. In clinical obstetrics, the gestational age is often estimated as the time from the last day of the last menstruation which is about 2 weeks before ovulation and fertilization. Pregnancy: Diagnosis, Physiology, and Care, starting at 4 weeks after birth
  • Follow-up exams weekly
• How to screen:
  •  Use indirect ophthalmoscopy or a RetCam digital camera
  • The aim is to look for the features that stage retinopathy Retinopathy Degenerative changes to the retina due to hypertension. Alport Syndrome.
  • Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship are classified into 2 categories:
    1. Infants with low risk 
    2. Infants with proliferative retinopathy Retinopathy Degenerative changes to the retina due to hypertension. Alport Syndrome who require laser treatment
  • Risk of progression is determined by:
    • Weight gain 
    • Serum levels of insulin-like growth factor 1 (IGF-1) 
    • Degree of aggressiveness of the retinopathy Retinopathy Degenerative changes to the retina due to hypertension. Alport Syndrome

Management

• Early stages ( stage 1 Stage 1 Trypanosoma brucei/African trypanosomiasis or 2 in zone I without plus disease OR stage 3 in zone II without plus disease) require close follow-up without intervention.
• Indications for treatment:
  • Any stage of retinopathy Retinopathy Degenerative changes to the retina due to hypertension. Alport Syndrome in zone I with plus disease
  • Stage 3 in zone I without plus disease
  • Stage 2 or 3 in zone II with plus disease
• Treatment options:
  • Cryotherapy Cryotherapy A form of therapy consisting in the local or general use of cold. The selective destruction of tissue by extreme cold or freezing is cryosurgery. Chondrosarcoma: done under general anesthesia General anesthesia Procedure in which patients are induced into an unconscious state through use of various medications so that they do not feel pain during surgery. Anesthesiology: History and Basic Concepts
  • Indirect laser photocoagulation
  • Anti-vascular endothelial growth factor drugs, such as intravitreal bevacizumab Bevacizumab An anti-vegf humanized murine monoclonal antibody. It inhibits vegf receptors and helps to prevent pathologic angiogenesis. Targeted and Other Nontraditional Antineoplastic Therapy
  • Vitrectomy Vitrectomy Removal of the whole or part of the vitreous body in treating endophthalmitis, diabetic retinopathy, retinal detachment, intraocular foreign bodies, and some types of glaucoma. Retinal Detachment for retinal detachment Retinal detachment Retinal detachment is the separation of the neurosensory retina from the retinal pigmented epithelium and choroid. Rhegmatogenous retinal detachment, the most common type, stems from a break in the retina, allowing fluid to accumulate in the subretinal space. Retinal Detachment

Differential Diagnosis

The following conditions are differential diagnoses for blindness in infancy:

• Cataracts: a condition defined as painless clouding or opacity Opacity Imaging of the Lungs and Pleura of the lens Lens A transparent, biconvex structure of the eye, enclosed in a capsule and situated behind the iris and in front of the vitreous humor (vitreous body). It is slightly overlapped at its margin by the ciliary processes. Adaptation by the ciliary body is crucial for ocular accommodation. Eye: Anatomy that leads to a decrease in vision Vision Ophthalmic Exam. Cataracts often develop slowly in one or both eyes Both Eyes Refractive Errors. Symptoms may include blurry or double vision Vision Ophthalmic Exam, trouble with bright lights, halos around light, faded colors, and trouble seeing at night. Ophthalmologic inspection Inspection Dermatologic Examination often shows darkening of or opacities in the red reflex Red Reflex Cataracts in Children. Slit-lamp examination Slit-Lamp Examination Blepharitis will show the extent and location of the cataract Cataract Partial or complete opacity on or in the lens or capsule of one or both eyes, impairing vision or causing blindness. The many kinds of cataract are classified by their morphology (size, shape, location) or etiology (cause and time of occurrence). Neurofibromatosis Type 2. Cataracts have a diverse etiology including TORCH infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease, trauma, side effects of glucocorticoids Glucocorticoids Glucocorticoids are a class within the corticosteroid family. Glucocorticoids are chemically and functionally similar to endogenous cortisol. There are a wide array of indications, which primarily benefit from the antiinflammatory and immunosuppressive effects of this class of drugs. Glucocorticoids, and radiation Radiation Emission or propagation of acoustic waves (sound), electromagnetic energy waves (such as light; radio waves; gamma rays; or x-rays), or a stream of subatomic particles (such as electrons; neutrons; protons; or alpha particles). Osteosarcoma.
• Retinal detachment Retinal detachment Retinal detachment is the separation of the neurosensory retina from the retinal pigmented epithelium and choroid. Rhegmatogenous retinal detachment, the most common type, stems from a break in the retina, allowing fluid to accumulate in the subretinal space. Retinal Detachment: the separation of the neurosensory retina Retina The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outermost layer is pigmented, whereas the inner nine layers are transparent. Eye: Anatomy from the retinal pigmented epithelium Epithelium The epithelium is a complex of specialized cellular organizations arranged into sheets and lining cavities and covering the surfaces of the body. The cells exhibit polarity, having an apical and a basal pole. Structures important for the epithelial integrity and function involve the basement membrane, the semipermeable sheet on which the cells rest, and interdigitations, as well as cellular junctions. Surface Epithelium: Histology. The retina Retina The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outermost layer is pigmented, whereas the inner nine layers are transparent. Eye: Anatomy is the innermost layer of the eye, containing cones and rods that are specialized sensory Sensory Neurons which conduct nerve impulses to the central nervous system. Nervous System: Histology organs used to detect light. Anything affecting the connection between the retina Retina The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outermost layer is pigmented, whereas the inner nine layers are transparent. Eye: Anatomy and the choroid Choroid The thin, highly vascular membrane covering most of the posterior of the eye between the retina and sclera. Eye: Anatomy can lead to photoreceptor ischemia Ischemia A hypoperfusion of the blood through an organ or tissue caused by a pathologic constriction or obstruction of its blood vessels, or an absence of blood circulation. Ischemic Cell Damage and painless vision Vision Ophthalmic Exam loss as a consequence.
• Retinoblastoma Retinoblastoma Retinoblastoma is a rare tumor but the most common primary intraocular malignancy of childhood. It is believed that the condition arises from a neuronal progenitor cell. Retinoblastoma can be heritable or non-heritable. Retinoblastoma: the most common primary intraocular malignancy Malignancy Hemothorax of childhood, accounting for 2% of malignant tumors in children. The condition typically presents as leukocoria Leukocoria Cataracts in Children (abnormal white reflection in the eye) in children under the age of 2 years. The disease may affect one or both eyes Both Eyes Refractive Errors and can appear sporadically or cumulatively in families. Untreated, the condition is fatal, but with age-appropriate treatment there is a > 95% survival rate.