**4.5 Retinal detachment**

In spite of treatment efforts, a number of prematurely born infants develop advanced ROP with retinal detachment. Accurate detection of retinal detachment is crucial in decision making process as well as in predicting future vision outcomes.

*Optical Coherence Tomography in Retinopathy of Prematurity DOI: http://dx.doi.org/10.5772/intechopen.110859*

Differentiation of retinoschisis from retinal detachment and determination of foveal involvement can be a difficult task. Likewise, the decision whether to intervene may be a great challenge. OCT has been shown the ability to assess the exact location of detachment, assess the degree of retinal elevation, estimate foveal involvement and distinguish retinal detachment from retinoschisis [10, 38–40]. Shallow retinal detachments that are not seen on indirect ophthalmoscopy also can be detected earlier on OCT imaging [41]. Detecting post-laser photocoagulation exudative retinal detachment using OCT has been reported as well [42].

#### **4.6 Plus disease**

Plus disease is defined as increased venous dilatation and arteriolar tortuosity of the posterior retinal vessels in at least two quadrants [43]. It is an important clinical sign of ROP used to identify patients that require treatment. OCT can provide further objective understanding of structural changes that occur in plus disease. Threedimensional reconstruction of OCT images can allow visualization of vessel tortuosity not only in two dimensions, but in the third dimension across the retinal depth as well [17]. Special OCT views such as Retinal Vessel Shadow View have been proposed for evaluation of plus disease [44]. Furthermore, OCT may detect vessel elevation, a feature that is known to be related to ROP severity [45].

With the aim of reducing the impact of individual OCT features and to ensure a more comprehensive evaluation of vascular changes, a Vascular Abnormality Score on OCT (VASO) was suggested (**Table 1**). In this scoring system more uncommon features are more heavily weighted. Thus, uncommon findings have more impact on VASO score. A cut-off value of 2 was proposed. Subjects in the plus disease group had significantly higher VASO than scores in the control group. The mean difference in VASO score was larger when imaging was performed before 37 weeks corrected gestational age [45].

#### **4.7 Macular edema**

Macular edema has been a subject of recent research thanks to the ease of its detection by OCT (**Figure 2**). This is a feature that is usually not detected by traditional


#### **Table 1.**

*Vascular abnormality score on optical coherence tomography (VASO).*

*Optical Coherence Tomography – Developments and Innovations in Ophthalmology*

#### **Figure 2.**

*Macular edema. Foveal OCT B-scan image in an eye of a preterm infant born at 28 weeks gestational age (birth weight 1220 g) imaged at 32 weeks postmenstrual age. Macular edema was only observed in the inner nuclear layer at the parafovea (A). Foveal OCT B-scan image in an eye of a preterm infant born at 25 weeks gestational age (birth weight 605 g) imaged at 42 weeks postmenstrual age. Macular edema was also only observed in the inner nuclear layer but at both fovea and parafovea (B). Yellow asterisk is located at within a cystoid space at fovea.*

indirect ophthalmoscopy, and it often remains undiagnosed during infancy. Different studies use different nomenclature for this feature, which include "retinal cystoid structures" [29], "foveal/macular changes" [12], "cystoid macular changes" [46] and "macular edema of prematurity" (MEOP). This phenomenon frequently resolves spontaneously [17]. Maldonado et al. found cystoid macular edema (CME) in 50% of premature neonates imaged between 31 and 36 weeks of corrected gestational age. CME persisted in all subjects through 36 weeks of corrected gestational age. The study was not

#### *Optical Coherence Tomography in Retinopathy of Prematurity DOI: http://dx.doi.org/10.5772/intechopen.110859*

designed for long term follow up, however the resolution of CME was observed in 9 out of 17 subjects after 37 weeks corrected gestational age [47]. Vinekar et al. performed a study on 74 patients and CME was found in 16% of patients. The resolution was reported in 100% of patients imaged at 52 weeks of corrected gestational age [12].

CME seen in premature infants is different than CME seen in adult patients. Thus, in premature infants CME is located exclusively in inner nuclear layer while in adults cystoid structures may be found in multiple retinal layers [47, 48]. Adult CME is caused by both extracellular accumulation of fluid as well as intracellular swelling of Muller cells whereas infantile CME may be represented principally by the swelling of Muller cells, or potentially extracellular fluid accumulation that is bridged by Muller cells [47, 49].

The exact etiology of CME encountered in premature infants is not precisely known. Several hypotheses have been suggested. Maldonado et al. and Vinekar et al. have proposed that CME develops as a result of the effects of neurohumoral factors, primarily vascular endothelial growth factor (VEGF). Edema may be attributed to increased vascular permeability that is caused by increased concentration of VEGF [12, 47]. This theory is plausible given the role of VEGF in the pathogenesis of ROP. Among 27 different cytokines measured in the vitreous body VEGF was found to be of the highest concentrations in patients with advanced ROP compared to controls [50]. Nevertheless, it was observed that CME might develop after intravitreal injection of bevacizumab, a VEGF inhibitor [46]. This led to a thought that other pathogenetic factors, such as mechanical traction exerted on the macula, might be involved. Tractional pathogenesis theory is also supported by an association of CME with the development of vitreous bands [30]. Furthermore, Erol et al. have suggested that lower retina pigment epithelium cell density might promote the development of CME [51].

As noted earlier, CME is a common finding in premature neonates, and its mere presence may not be necessarily associated with ROP. It may represent a non-pathologic transient stage of foveal development. Currently, there is no consensus whether the severity of CME is correlated with ROP. Dubis et al. reported in their study that severity of CME does not appear to be correlated with ROP stage [46]. However, greater severity of CME as evidenced by increased central foveal thickness, inner nuclear layer and fovea-to-parafoveal thickness ratio has been found by Maldonado et al. to be linked with higher ROP stage, presence of plus disease and the need for laser photocoagulation [47]. Similarly, Erol et al. reported that frequency and severity of CME go up with increasing ROP stage [51]. As the retinal changes have been found to correlate with gestational age and birth weight, it still continues to be unclear if those findings are due to preterm birth alone or are in connection with the effects of ROP and its management [52]. Other concomitant systemic factors may influence the development of CME. Among these factors are hypo- and hyperoxia, acidosis, arterial hypotension, presence of hemodynamically significant patent ductus arteriosus, infection, intraventricular hemorrhage, necrotizing enterocolitis, transfusion of blood products and apnea of prematurity [46]. However, Maldonado et al. made an attempt to correlate some of these factors (specifically Apgar scores at 1 and 5 minutes of life, PDA ligation, culture-proven sepsis, surgical necrotizing enterocolitis, presence of intraventricular hemorrhage, periventricular leukomalacia, bronchopulmonary dysplasia, and hydrocephalus) with CME and could not establish the association [47].

Anwar et al. reported in their study a correlation between foveal width and retinopathy of prematurity. The foveal width was increasing in the ROP group and decreasing in the non-ROP group. This difference of trajectory was found to be independent of gestational age and birth weight – variables that are certainly concurrent with the extent of prematurity. This difference was more apparent particularly at earlier corrected

gestational age. This phenomenon has the potential to be of utility when differentiating between premature infants that need further ROP screening from those that do not. Also, it has the potential to be used as a predictor of ROP that requires treatment [53].

Another possible association that might be of interest is the correlation of CME with neurodevelopmental outcomes in prematurely born children. Rothman et al. studied neurodevelopmental outcomes in 53 very preterm infants at 18 to 24 corrected gestational age. Infants who had CME detected during routine ROP screening eye examinations were found to have poorer language and motor skills on Bayley Scales for Infant and Toddler development when compared to the infants who did not have CME [54]. Thereby, detection and evaluation of CME using OCT imaging have the potential to serve as the predictor of neurodevelopmental outcomes in prematurely born infants.
