Background: For normally sighted readers, word neighborhood size (i.e., the total number of words that can be formed from a single word by changing only one letter) has a facilitator effect on word recognition. When reading with central field loss (CFL), however, individual letters may not be correctly identified, leading to possible misidentifications and a reverse neighborhood size effect. Here we investigate this inhibitory effect of word neighborhood size on reading performance and whether it is modulated by word predictability and reading proficiency. Methods: Nineteen patients with binocular CFL from 32 to 89 years old (mean ± SD = 75 ± 15) read short sentences presented with the self-paced reading paradigm. Accuracy and reading time were measured for each target word read, along with its predictability, i.e., its probability of occurrence following the two preceding words in the sentence using a trigram analysis. Linear mixed effects models were then fit to estimate the individual contributions of word neighborhood size, predictability, frequency and length on accuracy and reading time, while taking into account patients’ reading proficiency. Results: For the less proficient readers who quit reading on a daily basis, we found that the effect of neighborhood size was reversed compared to normal readers and of higher amplitude than the effect of frequency. Furthermore, this inhibitory effect is of greater amplitude (up to 50% decrease in reading speed) when a word is not easily predictable because its chances to occur after the two preceding words in a specific sentence are rather low. Conclusion: Severely impaired patients with CFL often quit reading on a daily basis because this task becomes simply too exhausting. Based on our results, we envision lexical text simplification as a new alternative to promote decisive rehabilitation in these patients. By increasing reading accessibility for those who struggle the most, text simplification might be used as an efficient readaptive tool and daily reading assistive technology, fostering overall reading ability and fluency through increased practice.